Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
May-2021 Volume 58 Issue 5

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2021 Volume 58 Issue 5

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review)

  • Authors:
    • Danhua Wang
    • Yiwen Sang
    • Tao Sun
    • Piaoping Kong
    • Lingyu Zhang
    • Yibei Dai
    • Ying Cao
    • Zhihua Tao
    • Weiwei Liu
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 20
    |
    Published online on: March 10, 2021
       https://doi.org/10.3892/ijo.2021.5200
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

MicroRNAs (miRNAs/miRs) are a class of small non‑coding RNAs that maintain the precise balance of various physiological processes through regulating the function of target mRNAs. Dysregulation of miRNAs is closely associated with various types of human cancer. miR‑222‑3p is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in tumor occurrence and progression. miR‑222‑3p in human biofluids, such as urine and plasma, may be a potential biomarker for the early diagnosis of tumors. In addition, miR‑222‑3p acts as a prognostic factor for the survival of patients with cancer. The present review first summarizes and discusses the role of miR‑222‑3p as a biomarker for diverse types of cancers, and then focuses on its essential roles in tumorigenesis, progression, metastasis and chemoresistance. Finally, the current understanding of the regulatory mechanisms of miR‑222‑3p at the molecular level are summarized. Overall, the current evidence highlights the crucial role of miR‑222‑3p in cancer diagnosis, prognosis and treatment.
View Figures

Figure 1

Figure 2

View References

1 

Orso F, Quirico L, Dettori D, Coppo R, Virga F, Ferreira LC, Paoletti C, Baruffaldi D, Penna E and Taverna D: Role of miRNAs in tumor and endothelial cell interactions during tumor progression. Semin Cancer Biol. 60:214–224. 2020. View Article : Google Scholar

2 

Iwakawa HO and Tomari Y: The functions of MicroRNAs: mRNA decay and translational repression. Trends Cell Biol. 25:651–665. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Wightman B, Ha I and Ruvkun G: Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 75:855–862. 1993. View Article : Google Scholar : PubMed/NCBI

4 

Rupaimoole R, Calin GA, Lopez-Berestein G and Sood AK: miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 6:235–246. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Gebert LFR and MacRae IJ: Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. 20:21–37. 2019. View Article : Google Scholar :

6 

Treiber T, Treiber N and Meister G: Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol. 20:5–20. 2019. View Article : Google Scholar

7 

Ha M and Kim VN: Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 15:509–524. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K and Shiekhattar R: TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 436:740–744. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Zhao JJ, Chu ZB, Hu Y, Lin J, Wang Z, Jiang M, Chen M, Wang X, Kang Y, Zhou Y, et al: Targeting the miR-221-222/PUMA/BAK/BAX pathway abrogates dexamethasone resistance in multiple myeloma. Cancer Res. 75:4384–4397. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Chang KW, Kao SY, Wu YH, Tsai MM, Tu HF, Liu CJ, Lui MT and Lin SC: Passenger strand miRNA miR-31* regulates the phenotypes of oral cancer cells by targeting RhoA. Oral Oncol. 49:27–33. 2013. View Article : Google Scholar

11 

Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K and Kawada N: MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 61:1600–1609. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Yasmeen S, Kaur S, Mirza AH, Brodin B, Pociot F and Kruuse C: miRNA-27a-3p and miRNA-222-3p as novel modulators of phosphodiesterase 3a (PDE3A) in cerebral microvascular endothelial cells. Mol Neurobiol. 56:5304–5314. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Gulluoglu S, Tuysuz EC, Kuskucu A, Ture U, Atalay B, Sahin F and Bayrak OF: The potential function of microRNA in chordomas. Gene. 585:76–83. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Wu C, Liu Z, Ma L, Pei C, Qin L, Gao N, Li J and Yin Y: MiRNAs regulate oxidative stress related genes via binding to the 3'UTR and TATA-box regions: A new hypothesis for cataract pathogenesis. BMC Ophthalmol. 17:2–8. 2017. View Article : Google Scholar

15 

Verjans R, Peters T, Beaumont FJ, van Leeuwen R, van Herwaarden T, Verhesen W, Munts C, Bijnen M, Henkens M, Diez J, et al: MicroRNA-221/222 family counteracts myocardial fibrosis in pressure overload-induced heart failure. Hypertension. 71:280–288. 2018. View Article : Google Scholar

16 

Wei F, Ma C, Zhou T, Dong X, Luo Q, Geng L, Ding L, Zhang Y, Zhang L, Li N, et al: Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p. Mol Cancer. 16:132–147. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Coarfa C, Fiskus W, Eedunuri VK, Rajapakshe K, Foley C, Chew SA, Shah SS, Geng C, Shou J, Mohamed JS, et al: Comprehensive proteomic profiling identifies the androgen receptor axis and other signaling pathways as targets of microRNAs suppressed in metastatic prostate cancer. Oncogene. 35:2345–2356. 2016. View Article : Google Scholar

18 

Liu L, Wang HJ, Meng T, Lei C, Yang XH, Wang QS, Jin B and Zhu JF: lncRNA GAS5 inhibits cell migration and invasion and promotes autophagy by targeting miR-222-3p via the GAS5/PTEN-signaling pathway in CRC. Mol Ther Nucleic Acids. 17:644–656. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Jafri MA, Al-Qahtani MH and Shay JW: Role of miRNAs in human cancer metastasis: Implications for therapeutic intervention. Semin Cancer Biol. 44:117–131. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Alves Dos Santos K, Clemente Dos Santos IC, Santos Silva C, Gomes Ribeiro H, de Farias Domingos I and Nogueira Silbiger V: Circulating exosomal miRNAs as biomarkers for the diagnosis and prognosis of Colorectal Cancer. 22:3462020.

22 

Fong M, Yan W, Ghassemian M, Wu X, Zhou X, Cao M, Jiang L, Wang J, Liu X, Zhang J and Wang SJ: Cancer-secreted miRNAs regulate amino-acid-induced mTORC1 signaling and fibroblast protein synthesis. EMBO Rep. 22:e512392020.PubMed/NCBI

23 

Wang X, Liao X, Huang K, Zeng X, Liu Z, Zhou X, Yu T, Yang C, Yu L, Wang Q, et al: Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma. J Cancer. 10:2520–2533. 2019. View Article : Google Scholar : PubMed/NCBI

24 

Wang H, Deng Z, Chen X, Cai J, Ma T, Zhong Q, Li R, Li L and Li T: Downregulation of miR-222-3p reverses doxorubicin-resistance in LoVo cells through upregulating forkhead box protein P2 (FOXP2) protein. Med Sci Monit. 25:2169–2178. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Guo J, Liu Q, Li Z, Guo H, Bai C and Wang F: miR-222-3p promotes osteosarcoma cell migration and invasion through targeting TIMP3. Onco Targets Ther. 11:8643–8653. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Liu B, Che Q, Qiu H, Bao W, Chen X, Lu W, Li B and Wan X: Elevated MiR-222-3p promotes proliferation and invasion of endometrial carcinoma via targeting ERalpha. PLoS One. 9:e875632014. View Article : Google Scholar

27 

Ostenfeld MS, Jensen SG, Jeppesen DK, Christensen LL, Thorsen SB, Stenvang J, Hvam ML, Thomsen A, Mouritzen P, Rasmussen MH, et al: miRNA profiling of circulating EpCAM(+) extracellular vesicles: Promising biomarkers of colorectal cancer. J Extracell Vesicles. 5:3402–3417. 2016. View Article : Google Scholar

28 

Korabecna M, Koutova L and Tesarova P: The potential roles of vesicle-enclosed miRNAs in communication between macrophages and cancer cells in tumor microenvironment. Neoplasma. 64:406–411. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Gasparello J, Papi C, Allegretti M, Giordani E, Carboni F, Zazza S, Pescarmona E, Romania P, Giacomini P, Scapoli C, et al: A distinctive microRNA (miRNA) signature in the blood of colorectal cancer (CRC) patients at surgery. Cancers (Basel). 12:24102020. View Article : Google Scholar

30 

Pudova E, Krasnov G, Nyushko K, Kobelyatskaya A, Savvateeva M, Poloznikov A, Dolotkazin D, Klimina K, Guvatova Z, Simanovsky S, et al: miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer. BMC Med Genomics. 13(Suppl 8): S1292020. View Article : Google Scholar

31 

Jiang K, Li G, Chen W, Song L, Wei T, Li Z, Gong R, Lei J, Shi H and Zhu J: Plasma exosomal miR-146b-5p and miR-222-3p are potential biomarkers for lymph node metastasis in papillary thyroid carcinomas. Onco Targets Ther. 13:1311–1319. 2020. View Article : Google Scholar : PubMed/NCBI

32 

Fredsoe J, Rasmussen AKI, Mouritzen P, Borre M, Orntoft T and Sorensen KD: A five-microRNA model (pCaP) for predicting prostate cancer aggressiveness using cell-free urine. Int J Cancer. 145:2558–2567. 2019. View Article : Google Scholar : PubMed/NCBI

33 

Cheng Y, Cheng T, Zhao Y and Qu Y: HMGA1 exacerbates tumor progression by activating miR-222 through PI3K/Akt/MMP-9 signaling pathway in uveal melanoma. Cell Signal. 63:52019. View Article : Google Scholar

34 

Zhang XF, Ye Y and Zhao SJ: LncRNA Gas5 acts as a ceRNA to regulate PTEN expression by sponging miR-222-3p in papillary thyroid carcinoma. Oncotarget. 9:3519–3530. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Tan X, Tang H, Bi J, Li N and Jia Y: MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in gastric cancer. J Cell Biochem. 119:5153–5162. 2018. View Article : Google Scholar

36 

Ma S, Kong S, Gu X, Xu Y, Tao M, Shen L, Shen X and Ju S: As a biomarker for gastric cancer, circPTPN22 regulates the progression of gastric cancer through the EMT pathway. Cancer Cell Int. 21:442021. View Article : Google Scholar : PubMed/NCBI

37 

Fu X, Li Y, Alvero A, Li J, Wu Q, Xiao Q, Peng Y, Hu Y, Li X, Yan W, et al: MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival. Oncotarget. 7:80633–80654. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Rosignolo F, Memeo L, Monzani F, Colarossi C, Pecce V, Verrienti A, Durante C, Grani G, Lamartina L, Forte S, et al: MicroRNA-based molecular classification of papillary thyroid carcinoma. Int J Oncol. 50:1767–1777. 2017. View Article : Google Scholar : PubMed/NCBI

39 

Di Fazio P, Montalbano R, Neureiter D, Alinger B, Schmidt A, Merkel AL, Quint K and Ocker M: Downregulation of HMGA2 by the pan-deacetylase inhibitor panobinostat is dependent on hsa-let-7b expression in liver cancer cell lines. Exp Cell Res. 318:1832–1843. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Jahanbani I, Al-Abdallah A, Ali RH, Al-Brahim N and Mojiminiyi O: Discriminatory miRNAs for the management of papillary thyroid carcinoma and noninvasive follicular thyroid neoplasms with papillary-like nuclear features. Thyroid. 28:319–327. 2018. View Article : Google Scholar : PubMed/NCBI

41 

Denaro M, Ugolini C, Poma AM, Borrelli N, Materazzi G, Piaggi P, Chiarugi M, Miccoli P, Vitti P and Basolo F: Differences in miRNA expression profiles between wild-type and mutated NIFTPs. Endocr Relat Cancer. 24:543–553. 2017. View Article : Google Scholar : PubMed/NCBI

42 

Borrelli N, Denaro M, Ugolini C, Poma AM, Miccoli M, Vitti P, Miccoli P and Basolo F: miRNA expression profiling of 'noninvasive follicular thyroid neoplasms with papillary-like nuclear features' compared with adenomas and infiltrative follicular variants of papillary thyroid carcinomas. Mod Pathol. 30:39–51. 2017. View Article : Google Scholar

43 

de Conti A, Ortega JF, Tryndyak V, Dreval K, Moreno FS, Rusyn I, Beland FA and Pogribny IP: MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis. Oncotarget. 8:88517–88528. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Kim BH, Hong SW, Kim A, Choi SH and Yoon SO: Prognostic implications for high expression of oncogenic microRNAs in advanced gastric carcinoma. J Surg Oncol. 107:505–510. 2013. View Article : Google Scholar

45 

Zhang L, Huang Z, Zhang H, Zhu M, Zhu W, Zhou X and Liu P: Prognostic value of candidate microRNAs in gastric cancer: A validation study. Cancer Biomark. 18:221–230. 2017. View Article : Google Scholar

46 

Rinnerthaler G, Hackl H, Gampenrieder SP, Hamacher F, Hufnagl C, Hauser-Kronberger C, Zehentmayr F, Fastner G, Sedlmayer F, Mlineritsch B and Greil R: miR-16-5p is a stably-expressed house-keeping MicroRNA in breast cancer tissues from primary tumors and from metastatic sites. Int J Mol Sci. 17:156–167. 2016. View Article : Google Scholar

47 

Fredsoe J, Rasmussen AKI, Thomsen AR, Mouritzen P, Hoyer S, Borre M, Orntoft TF and Sorensen KD: Diagnostic and prognostic MicroRNA biomarkers for prostate cancer in cell-free urine. Eur Urol Focus. 4:825–833. 2018. View Article : Google Scholar

48 

Fang R, Zhu Y, Hu L, Khadka VS, Ai J, Zou H, Ju D, Jiang B, Deng Y and Hu X: Plasma MicroRNA pair panels as novel biomarkers for detection of early stage breast cancer. Front Physiol. 9:1879–1880. 2018. View Article : Google Scholar

49 

Fu Z, Qian F, Yang X, Jiang H, Chen Y and Liu S: Circulating miR-222 in plasma and its potential diagnostic and prognostic value in gastric cancer. Med Oncol. 31:164–175. 2014. View Article : Google Scholar : PubMed/NCBI

50 

Chang YA, Weng SL, Yang SF, Chou CH, Huang WC, Tu SJ, Chang TH, Huang CN, Jong YJ and Huang HD: A Three-MicroRNA signature as a potential biomarker for the early detection of oral cancer. Int J Mol Sci. 19:7582018. View Article : Google Scholar

51 

Fredsoe J, Rasmussen AKI, Laursen EB, Cai Y, Howard KA, Pedersen BG, Borre M, Mouritzen P, Orntoft T and Sorensen KD: Independent validation of a diagnostic noninvasive 3-MicroRNA ratio model (uCaP) for prostate cancer in cell-free urine. Clin Chem. 65:540–548. 2019. View Article : Google Scholar

52 

Uchino K, Takeshita F, Takahashi RU, Kosaka N, Fujiwara K, Naruoka H, Sonoke S, Yano J, Sasaki H, Nozawa S, et al: Therapeutic effects of microRNA-582-5p and -3p on the inhibition of bladder cancer progression. Mol Ther. 21:610–619. 2013. View Article : Google Scholar : PubMed/NCBI

53 

Tan X, Tang H, Bi J, Li N and Jia Y: MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in gastric cancer. J Cell Biochem. 119:5153–5162. 2018. View Article : Google Scholar

54 

Rosignolo F, Sponziello M, Giacomelli L, Russo D, Pecce V, Biffoni M, Bellantone R, Lombardi CP, Lamartina L, Grani G, et al: Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up. J Endocr Soc. 1:3–13. 2017.PubMed/NCBI

55 

Ulivi P, Petracci E, Marisi G, Baglivo S, Chiari R, Billi M, Canale M, Pasini L, Racanicchi S, Vagheggini A, et al: Prognostic role of circulating miRNAs in Early-stage non-small cell lung cancer. J Clin Med. 8:131–142. 2019. View Article : Google Scholar :

56 

Wang Y, Yin W, Lin Y, Yin K, Zhou L, Du Y, Yan T and Lu J: Downregulated circulating microRNAs after surgery: Potential noninvasive biomarkers for diagnosis and prognosis of early breast cancer. Cell Death Discov. 4:2–8. 2018. View Article : Google Scholar

57 

Kara M, Yumrutas O, Ozcan O, Celik OI, Bozgeyik E, Bozgeyik I and Tasdemir S: Differential expressions of cancer-associated genes and their regulatory miRNAs in colorectal carcinoma. Gene. 567:81–86. 2015. View Article : Google Scholar : PubMed/NCBI

58 

Spindler KL, Pallisgaard N, Vogelius I and Jakobsen A: Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan. Clin Cancer Res. 18:1177–1185. 2012. View Article : Google Scholar : PubMed/NCBI

59 

Domingo E, Camps C, Kaisaki PJ, Parsons MJ, Mouradov D, Pentony MM, Makino S, Palmieri M, Ward RL, Hawkins NJ, et al: Mutation burden and other molecular markers of prognosis in colorectal cancer treated with curative intent: Results from the QUASAR 2 clinical trial and an Australian community-based series. Lancet Gastroenterol Hepatol. 3:635–643. 2018. View Article : Google Scholar : PubMed/NCBI

60 

Zhao H, Shen J, Hodges TR, Song R, Fuller GN and Heimberger AB: Serum microRNA profiling in patients with glioblastoma: A survival analysis. Mol Cancer. 16:59–70. 2017. View Article : Google Scholar : PubMed/NCBI

61 

Cooper J and Giancotti FG: Integrin signaling in cancer: Mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell. 35:347–367. 2019. View Article : Google Scholar : PubMed/NCBI

62 

Friedmann Angeli JP, Krysko DV and Conrad M: Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer. 19:405–414. 2019. View Article : Google Scholar : PubMed/NCBI

63 

Tooker P, Yen WC, Ng SC, Negro-Vilar A and Hermann TW: Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification. Cancer Res. 67:4425–4433. 2007. View Article : Google Scholar : PubMed/NCBI

64 

Alvarez-Garcia I and Miska EA: MicroRNA functions in animal development and human disease. Development. 132:4653–4662. 2005. View Article : Google Scholar : PubMed/NCBI

65 

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI

66 

Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F, Alder H, Condorelli G, et al: EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med. 18:74–82. 2011. View Article : Google Scholar : PubMed/NCBI

67 

Liu S, Sun X, Wang M, Hou Y, Zhan Y, Jiang Y, Liu Z, Cao X, Chen P, Chen X, et al: A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NFκB and STAT3 in colorectal cancer cells. Gastroenterology. 147:847–859.e11. 2014. View Article : Google Scholar

68 

Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S and Zucman-Rossi J: MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology. 47:1955–1963. 2008. View Article : Google Scholar : PubMed/NCBI

69 

Li Z, Yu Z, Meng X, Zhou S, Xiao S, Li X, Liu S and Yu P: Long noncoding RNA GAS5 impairs the proliferation and invasion of endometrial carcinoma induced by high glucose via targeting miR-222-3p/p27. Am J Transl Res. 11:2413–2421. 2019.PubMed/NCBI

70 

Paquet-Fifield S, Koh SL, Cheng L, Beyit LM, Shembrey C, Molck C, Behrenbruch C, Papin M, Gironella M, Guelfi S, et al: Tight junction protein Claudin-2 promotes Self-renewal of human colorectal cancer Stem-like cells. Cancer Res. 78:2925–2938. 2018. View Article : Google Scholar : PubMed/NCBI

71 

Polk DB and Peek RM Jr: Helicobacter pylori: Gastric cancer and beyond. Nat Rev Cancer. 10:403–414. 2010. View Article : Google Scholar : PubMed/NCBI

72 

Ishiguro H, Kimura M and Takeyama H: Role of microRNAs in gastric cancer. World J Gastroenterol. 20:5694–5699. 2014. View Article : Google Scholar : PubMed/NCBI

73 

Ebert MS and Sharp PA: Roles for microRNAs in conferring robustness to biological processes. Cell. 149:515–524. 2012. View Article : Google Scholar : PubMed/NCBI

74 

Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X, Coppola D and Cheng JQ: MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem. 291:31079–31086. 2016. View Article : Google Scholar

75 

Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, et al: miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 16:498–509. 2009. View Article : Google Scholar : PubMed/NCBI

76 

Sun K, Wang W, Zeng JJ, Wu CT, Lei ST and Li GX: MicroRNA-221 inhibits CDKN1C/p57 expression in human colorectal carcinoma. Acta Pharmacol Sin. 32:375–384. 2011. View Article : Google Scholar : PubMed/NCBI

77 

Zhang Y, Ma T, Yang S, Xia M, Xu J, An H, Yang Y and Li S: High-mobility group A1 proteins enhance the expression of the oncogenic miR-222 in lung cancer cells. Mol Cell Biochem. 357:363–371. 2011. View Article : Google Scholar : PubMed/NCBI

78 

Ying SY, Chang DC, Miller JD and Lin SL: The microRNA: Overview of the RNA gene that modulates gene functions. Methods Mol Biol. 342:1–18. 2006.PubMed/NCBI

79 

Fuse M, Kojima S, Enokida H, Chiyomaru T, Yoshino H, Nohata N, Kinoshita T, Sakamoto S, Naya Y, Nakagawa M, et al: Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer. J Hum Genet. 57:691–699. 2012. View Article : Google Scholar : PubMed/NCBI

80 

Ottley EC, Nicholson HD and Gold EJ: Activin A regulates microRNAs and gene expression in LNCaP cells. Prostate. 76:951–963. 2016. View Article : Google Scholar : PubMed/NCBI

81 

Tong AW, Fulgham P, Jay C, Chen P, Khalil I, Liu S, Senzer N, Eklund AC, Han J and Nemunaitis J: MicroRNA profile analysis of human prostate cancers. Cancer Gene Ther. 16:206–216. 2009. View Article : Google Scholar

82 

Ottley EC, Nicholson HD and Gold EJ: Activin A regulates microRNAs and gene expression in LNCaP cells. Prostate. 76:951–963. 2016. View Article : Google Scholar : PubMed/NCBI

83 

Xu G, Wu J, Zhou L, Chen B, Sun Z, Zhao F and Tao Z: Characterization of the small RNA transcriptomes of androgen dependent and independent prostate cancer cell line by deep sequencing. PLoS One. 5:e155192010. View Article : Google Scholar : PubMed/NCBI

84 

Rihani A, Van Goethem A, Ongenaert M, De Brouwer S, Volders PJ, Agarwal S, De Preter K, Mestdagh P, Shohet J, Speleman F, et al: Genome wide expression profiling of p53 regulated miRNAs in neuroblastoma. Sci Rep. 5:9027–9044. 2015. View Article : Google Scholar : PubMed/NCBI

85 

Narrandes S and Xu W: Gene expression detection assay for cancer clinical use. J Cancer. 9:2249–2265. 2018. View Article : Google Scholar : PubMed/NCBI

86 

Bourboulia D and Stetler-Stevenson WG: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Semin Cancer Biol. 20:161–168. 2010. View Article : Google Scholar : PubMed/NCBI

87 

Liu W, Wang X, Wang Y, Dai Y, Xie Y, Ping Y, Yin B, Yu P, Liu Z, Duan X, et al: SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing. EMT J Exp Clin Cancer Res. 37:732018. View Article : Google Scholar

88 

Liu W, Wang X, Liu Z, Wang Y, Yin B, Yu P, Duan X, Liao Z, Chen Y, Liu C, et al: SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway. Br J Cancer. 117:1139–1153. 2017. View Article : Google Scholar : PubMed/NCBI

89 

Indran IR, Tufo G, Pervaiz S and Brenner C: Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim Biophys Acta. 1807:735–745. 2011. View Article : Google Scholar : PubMed/NCBI

90 

Mavrogiannis A, Kokkinopoulou I, Kontos C and Sideris DJ: Effect of vinca alkaloids on the expression levels of microRNAs targeting apoptosis-related genes in breast cancer cell lines. Curr Pharm Biotechnol. 19:1076–1086. 2018. View Article : Google Scholar : PubMed/NCBI

91 

Jacob H, Stanisavljevic L, Storli KE, Hestetun KE, Dahl O and Myklebust MP: Identification of a sixteen-microRNA signature as prognostic biomarker for stage II and III colon cancer. Oncotarget. 8:87837–87847. 2017. View Article : Google Scholar : PubMed/NCBI

92 

Tan HY, Wang N, Lam W, Guo W, Feng Y and Cheng YC: Targeting tumour microenvironment by tyrosine kinase inhibitor. Mol Cancer. 17:43–52. 2018. View Article : Google Scholar : PubMed/NCBI

93 

Vuong L, Kotecha RR, Voss MH and Hakimi AA: Tumor microenvironment dynamics in clear-cell renal cell carcinoma. Cancer Discov. 9:1349–1357. 2019. View Article : Google Scholar : PubMed/NCBI

94 

Vitale I, Manic G, Coussens LM, Kroemer G and Galluzzi L: Macrophages and metabolism in the tumor microenvironment. Cell Metab. 30:36–50. 2019. View Article : Google Scholar : PubMed/NCBI

95 

Zhou S, Liu R, Yuan K, Yi T, Zhao X, Huang C and Wei Y: Proteomics analysis of tumor microenvironment: Implications of metabolic and oxidative stresses in tumorigenesis. Mass Spectrom Rev. 32:267–311. 2013. View Article : Google Scholar

96 

Ying X, Wu Q, Wu X, Zhu Q and Wang X, Jiang L, Chen X and Wang X: Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macro-phages. Oncotarget. 7:43076–43087. 2016. View Article : Google Scholar : PubMed/NCBI

97 

Cabibbo G, Celsa C, Calvaruso V, Petta S, Cacciola I, Cannavo MR, Madonia S, Rossi M, Magro B, Rini F, et al: Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients. J Hepatol. 71:265–273. 2019. View Article : Google Scholar : PubMed/NCBI

98 

Degasperi E, D'Ambrosio R, Iavarone M, Sangiovanni A, Aghemo A, Soffredini R, Borghi M, Lunghi G, Colombo M and Lampertico P: Factors associated with increased risk of de novo or recurrent hepatocellular carcinoma in patients with cirrhosis treated with direct-acting antivirals for HCV infection. Clin Gastroenterol Hepatol. 17:1183–1191.e7. 2019. View Article : Google Scholar : PubMed/NCBI

99 

Santangelo L, Bordoni V, Montaldo C, Cimini E, Zingoni A, Battistelli C, D'Offizi G, Capobianchi MR, Santoni A, Tripodi M and Agrati C: Hepatitis C virus direct-acting antivirals therapy impacts on extracellular vesicles microRNAs content and on their immunomodulating properties. Liver Int. 38:1741–1750. 2018. View Article : Google Scholar : PubMed/NCBI

100 

Varchetta S, Mele D, Mantovani S, Oliviero B, Cremonesi E, Ludovisi S, Michelone G, Alessiani M, Rosati R, Montorsi M and Mondelli MU: Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection. Hepatology. 56:841–849. 2012. View Article : Google Scholar : PubMed/NCBI

101 

van der Meer AJ, Feld JJ, Hofer H, Almasio PL, Calvaruso V, Fernandez-Rodriguez CM, Aleman S, Ganne-Carrie N, D'Ambrosio R, Pol S, et al: Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication. J Hepatol. 66:485–493. 2017. View Article : Google Scholar

102 

Fugier E, Marche H, Thélu MA, Macek Jilková Z, Van Campenhout N, Dufeu-Duchesne T, Leroy V, Zarski JP, Sturm N, Marche PN and Jouvin-Marche E: Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C. PLoS One. 9:e956142014. View Article : Google Scholar : PubMed/NCBI

103 

Tölle A, Jung K, Friedersdorff F, Maxeiner A, Lein M, Fendler A and Stephan C: The discriminative ability of Prostate Health Index to detect prostate cancer is enhanced in combination with miR-222-3p. Cancer Biomark. Dec 15–2020.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI

104 

Ryu K, Lee J, Choi M, Yoon S, Cho J, Ko Y, Shim J, Kim W, Park C and Kim SJ: Serum-derived exosomal MicroRNA profiles can predict poor survival outcomes in patients with extranodal natural Killer/T-cell lymphoma. Cancers (Basel). 12:35482020. View Article : Google Scholar

105 

Zhai S, Xu Z, Xie J, Zhang J, Wang X, Peng C, Li H, Chen H, Shen B and Deng X: Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1. Oncogene. 40:277–291. 2021. View Article : Google Scholar :

106 

Lu B, Sheng Y, Zhang J, Zheng Z and Ji L: The altered microRNA profile in andrographolide-induced inhibition of hepatoma tumor growth. Gene. 588:124–133. 2016. View Article : Google Scholar : PubMed/NCBI

107 

Gumbiner BM and Kim NG: The Hippo-YAP signaling pathway and contact inhibition of growth. J Cell Sci. 127:709–717. 2014. View Article : Google Scholar : PubMed/NCBI

108 

Panneerselvam J, Srivastava A, Muralidharan R, Wang Q, Zheng W, Zhao L, Chen A, Zhao YD, Munshi A and Ramesh R: IL-24 modulates the high mobility group (HMG) A1/miR222/AKT signaling in lung cancer cells. Oncotarget. 7:70247–70263. 2016. View Article : Google Scholar : PubMed/NCBI

109 

Ignacio C, Mooney SM and Middleton FA: Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment. Front Pediatr. 2:1032014. View Article : Google Scholar : PubMed/NCBI

110 

Théry C, Zitvogel L and Amigorena S: Exosomes: Composition, biogenesis and function. Nat Rev Immunol. 2:569–579. 2002. View Article : Google Scholar : PubMed/NCBI

111 

Pant S, Hilton H and Burczynski ME: The multifaceted exosome: Biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacol. 83:1484–1494. 2012. View Article : Google Scholar : PubMed/NCBI

112 

Kalluri R: The biology and function of exosomes in cancer. J Clin Invest. 126:1208–1215. 2016. View Article : Google Scholar : PubMed/NCBI

113 

Sun Z, Shi K, Yang S, Liu J, Zhou Q, Wang G, Song J, Li Z, Zhang Z and Yuan W: Effect of exosomal miRNA on cancer biology and clinical applications. Mol Cancer. 17:1472018. View Article : Google Scholar : PubMed/NCBI

114 

Han Z, Li Y, Zhang J, Guo C, Li Q, Zhang X, Lan Y, Gu W, Xing Z, Liang L, et al: Tumor-derived circulating exosomal miR-342-5p and miR-574-5p as promising diagnostic biomarkers for early-stage Lung Adenocarcino. Int J Med Sci. 17:1428–1438. 2020. View Article : Google Scholar :

115 

Ortega MM and Bouamar H: Guidelines on designing MicroRNA sponges: From construction to stable cell line. Methods Mol Biol. 1509:221–233. 2017. View Article : Google Scholar

116 

Wang Z: The guideline of the design and validation of MiRNA mimics. Methods Mol Biol. 676:211–223. 2011. View Article : Google Scholar

117 

Arroyo J, Gallichotte E and Tewari M: Systematic design and functional analysis of artificial microRNAs. Nucleic Acids Res. 42:6064–6077. 2014. View Article : Google Scholar : PubMed/NCBI

118 

Ganju A, Khan S, Hafeez BB, Behrman SW, Yallapu MM, Chauhan SC and Jaggi M: miRNA nanotherapeutics for cancer. Drug Discov Today. 22:424–432. 2017. View Article : Google Scholar :

119 

Chen Y, Gao DY and Huang L: In vivo delivery of miRNAs for cancer therapy: challenges and strategies. Adv Drug Deliv Rev. 81:128–141. 2015. View Article : Google Scholar

120 

Bofill-De Ros X and Gu S: Guidelines for the optimal design of miRNA-based shRNAs. Methods. 103:157–166. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang D, Sang Y, Sun T, Kong P, Zhang L, Dai Y, Cao Y, Tao Z and Liu W: Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review). Int J Oncol 58: 20, 2021.
APA
Wang, D., Sang, Y., Sun, T., Kong, P., Zhang, L., Dai, Y. ... Liu, W. (2021). Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review). International Journal of Oncology, 58, 20. https://doi.org/10.3892/ijo.2021.5200
MLA
Wang, D., Sang, Y., Sun, T., Kong, P., Zhang, L., Dai, Y., Cao, Y., Tao, Z., Liu, W."Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review)". International Journal of Oncology 58.5 (2021): 20.
Chicago
Wang, D., Sang, Y., Sun, T., Kong, P., Zhang, L., Dai, Y., Cao, Y., Tao, Z., Liu, W."Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review)". International Journal of Oncology 58, no. 5 (2021): 20. https://doi.org/10.3892/ijo.2021.5200
Copy and paste a formatted citation
x
Spandidos Publications style
Wang D, Sang Y, Sun T, Kong P, Zhang L, Dai Y, Cao Y, Tao Z and Liu W: Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review). Int J Oncol 58: 20, 2021.
APA
Wang, D., Sang, Y., Sun, T., Kong, P., Zhang, L., Dai, Y. ... Liu, W. (2021). Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review). International Journal of Oncology, 58, 20. https://doi.org/10.3892/ijo.2021.5200
MLA
Wang, D., Sang, Y., Sun, T., Kong, P., Zhang, L., Dai, Y., Cao, Y., Tao, Z., Liu, W."Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review)". International Journal of Oncology 58.5 (2021): 20.
Chicago
Wang, D., Sang, Y., Sun, T., Kong, P., Zhang, L., Dai, Y., Cao, Y., Tao, Z., Liu, W."Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review)". International Journal of Oncology 58, no. 5 (2021): 20. https://doi.org/10.3892/ijo.2021.5200
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team