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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
February-2022 Volume 25 Issue 2

Full Size Image

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
February-2022 Volume 25 Issue 2

Full Size Image

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
Article Open Access

CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS

  • Authors:
    • Jingjing Chen
    • Peng Shi
    • Jinghua Zhang
    • Yufeng Li
    • Jie Ma
    • Yudong Zhang
    • Hong Liu
  • View Affiliations / Copyright

    Affiliations: The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin 300060, P.R. China, The Second Department of Urology Surgery, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, Department of Breast Health Care, Maternal and Child Care Service Centre, Tangshan, Hebei 063000, P.R. China, Central Laboratory, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, The First Department of Breast Surgery, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, North China University of Science and Technology, Tangshan People's Hospital, Tangshan, Hebei 063210, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 51
    |
    Published online on: December 13, 2021
       https://doi.org/10.3892/mmr.2021.12567
  • 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

CircRNAs are associated with adriamycin (ADM) resistance in triple‑negative breast cancer (TNBC), but the mechanism is unknown. Reverse transcription‑quantitative PCR was applied to quantify circular RNA (circRNA)_0044556, microRNA (miR)‑145 and NRAS proto‑oncogene, GTPase (NRAS) in TNBC tissues and cells with or without ADM treatment. Following ADM treatment, the effects of circRNA_0044556 on the viability, ADM resistance, apoptosis and migration of TNBC cells were investigated by cell function experiments (Cell Counting Kit‑8, flow cytometry and Transwell assays). The targeting relationship between circRNA_0044556 and miR‑145 was investigated via bioinformatics analysis, dual‑luciferase reporter assay and RNA immunoprecipitation. The effects of the circRNA_0044556/miR‑145 axis on the TNBC cells were revealed by rescue experiments. Correlations among circRNA_0044556, miR‑145 and NRAS were analyzed by Pearson's correlation test. CircRNA_0044556 was highly expressed in TNBC tissues and cells with or without ADM‑resistance. The overexpression of circRNA_0044556 promoted cell viability, ADM‑resistance and migration, while inhibiting the apoptosis by sponging miR‑145. Upregulation of miR‑145 reversed the effects of circRNA_0044556 on the TNBC cells. CircRNA_0044556 was negatively correlated with miR‑145 yet positively correlated with NRAS, the target gene of miR‑145, in addition to the discovery suggesting the negative regulatory effects of circRNA_0044556 on miR‑145. CircRNA_0044556 diminished the sensitivity of TNBC cells to ADM via the miR‑145/NRAS axis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Zuo T, Zeng H, Li H, Liu S, Yang L, Xia C, Zheng R, Ma F, Liu L, Wang N, et al: The influence of stage at diagnosis and molecular subtype on breast cancer patient survival: A hospital-based multi-center study. Chin J Cancer. 36:842017. View Article : Google Scholar : PubMed/NCBI

2 

Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel Members, André F, et al: Tailoring therapies-improving the management of early breast cancer: St gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 26:1533–1546. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Kumar P and Aggarwal R: An overview of triple-negative breast cancer. Arch Gynecol Obstet. 293:247–269. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Parikh RR, Yang Q, Higgins SA and Haffty BG: Outcomes in young women with breast cancer of triple-negative phenotype: The prognostic significance of CK19 expression. Int J Radiat Oncol Biol Phys. 70:35–42. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Lehmann BD, Pietenpol JA and Tan AR: Triple-negative breast cancer: Molecular subtypes and new targets for therapy. Am Soc Clin Oncol Educ Book. e31–e39. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Gao D, Zhang X, Liu B, Meng D, Fang K, Guo Z and Li L: Screening circular RNA related to chemotherapeutic resistance in breast cancer. Epigenomics. 9:1175–1188. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Song J, Yin J, Bai Z, Zhang J, Meng H, Cai J, Deng W, Ma X and Zhang Z: The profile of serum microRNAs predicts prognosis for resected gastric cancer patients receiving platinum-based chemotherapy. Dig Dis Sci. 62:1223–1234. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Yang M, Li Y, Ruan Y, Lu Y, Lin D, Xie Y, Dong B, Dang Q and Quan C: CLDN6 enhances chemoresistance to ADM via AF-6/ERKs pathway in TNBC cell line MDAMB231. Mol Cell Biochem. 443:169–180. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Li Z, Chen Z, Hu G and Jiang Y: Roles of circular RNA in breast cancer: Present and future. Am J Transl Res. 11:3945–3954. 2019.PubMed/NCBI

10 

Jahani S, Nazeri E, Majidzadeh AK, Jahani M and Esmaeili R: Circular RNA; a new biomarker for breast cancer: A systematic review. J Cell Physiol. 235:5501–5510. 2020. View Article : Google Scholar : PubMed/NCBI

11 

Guo JU, Agarwal V, Guo H and Bartel DP: Expanded identification and characterization of mammalian circular RNAs. Genome Biol. 15:4092014. View Article : Google Scholar : PubMed/NCBI

12 

Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P and Wu M: CircRNA: Functions and properties of a novel potential biomarker for cancer. Mol Cancer. 16:942017. View Article : Google Scholar : PubMed/NCBI

13 

Shen Z, Zhou L, Zhang C and Xu J: Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel. Cancer Lett. 468:88–101. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Sang Y, Chen B, Song X, Li Y, Liang Y, Han D, Zhang N, Zhang H, Liu Y, Chen T, et al: circRNA_0025202 regulates tamoxifen sensitivity and tumor progression via regulating the miR-182-5p/FOXO3a axis in breast cancer. Mol Ther. 27:1638–1652. 2019. View Article : Google Scholar : PubMed/NCBI

15 

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Akram M and Siddiqui SA: Breast cancer management: Past, present and evolving. Indian J Cancer. 49:277–282. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Yin Y, Wang X, Li T, Ren Q, Li L, Sun X, Zhang B, Wang X, Han H, He Y, et al: MicroRNA-221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling. Cancer Med. 9:1544–1552. 2020. View Article : Google Scholar : PubMed/NCBI

19 

Vasan N, Baselga J and Hyman DM: A view on drug resistance in cancer. Nature. 575:299–309. 2019. View Article : Google Scholar : PubMed/NCBI

20 

Nikolaou M, Pavlopoulou A, Georgakilas AG and Kyrodimos E: The challenge of drug resistance in cancer treatment: A current overview. Clin Exp Metastasis. 35:309–318. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Liang Y, Song X, Li Y, Su P, Han D, Ma T, Guo R, Chen B, Zhao W, Sang Y, et al: circKDM4C suppresses tumor progression and attenuates doxorubicin resistance by regulating miR-548p/PBLD axis in breast cancer. Oncogene. 38:6850–6866. 2019. View Article : Google Scholar : PubMed/NCBI

22 

Dou D, Ren X, Han M, Xu X, Ge X, Gu Y, Wang X and Zhao S: CircUBE2D2 (hsa_circ_0005728) promotes cell proliferation, metastasis and chemoresistance in triple-negative breast cancer by regulating miR-512-3p/CDCA3 axis. Cancer Cell Int. 20:4542020. View Article : Google Scholar : PubMed/NCBI

23 

Jing L, Wu J, Tang X, Ma M, Long F, Tian B and Lin C: Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer. Cancer Cell Int. 20:4272020. View Article : Google Scholar : PubMed/NCBI

24 

Yamaguchi R, Lartigue L and Perkins G: Targeting Mcl-1 and other Bcl-2 family member proteins in cancer therapy. Pharmacol Therap. 195:13–20. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Tang YY, Zhao P, Zou TN, Duan JJ, Zhi R, Yang SY, Yang DC and Wang XL: Circular RNA hsa_circ_0001982 promotes breast cancer cell carcinogenesis through decreasing miR-143. DNA Cell Biol. 36:901–908. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Gao M, Miao L, Liu M, Li C, Yu C, Yan H, Yin Y, Wang Y, Qi X and Ren J: miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1. Oncotarget. 7:59714–59726. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Ding Y, Zhang C, Zhang J, Zhang N, Li T, Fang J, Zhang Y, Zuo F, Tao Z, Tang S, et al: miR-145 inhibits proliferation and migration of breast cancer cells by directly or indirectly regulating TGF-β1 expression. Int J Oncol. 50:1701–1710. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Chen S, Li F, Xu D, Hou K, Fang W and Li Y: The function of RAS mutation in cancer and advances in its drug research. Curr Pharm Des. 25:1105–1114. 2019. View Article : Google Scholar : PubMed/NCBI

29 

Druillennec S, Pouponnot C and Eychène A: NRAS-driven melanoma: A RAF can hide another. Mol Cell Oncol. 4:e13447582017. View Article : Google Scholar : PubMed/NCBI

30 

Banys-Paluchowski M, Milde-Langosch K, Fehm T, Witzel I, Oliveira-Ferrer L, Schmalfeldt B and Müller V: Clinical relevance of H-RAS, K-RAS, and N-RAS mRNA expression in primary breast cancer patients. Breast Cancer Res Treat. 179:403–414. 2020. View Article : Google Scholar : PubMed/NCBI

31 

Prior IA, Lewis PD and Mattos C: A comprehensive survey of Ras mutations in cancer. Cancer Res. 72:2457–2467. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Song YK, Wang Y, Wen YY, Zhao P and Bian ZJ: MicroRNA-22 suppresses breast cancer cell growth and increases paclitaxel sensitivity by targeting NRAS. Technol Cancer Res Treat. 17:15330338188099972018. View Article : Google Scholar : PubMed/NCBI

33 

Li X, Liu Y, Zhang X, Shen J, Xu R, Liu Y and Yu X: Circular RNA hsa_circ_0000073 contributes to osteosarcoma cell proliferation, migration, invasion and methotrexate resistance by sponging miR-145-5p and miR-151-3p and upregulating NRAS. Aging (Albany NY). 12:14157–14173. 2020. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen J, Shi P, Zhang J, Li Y, Ma J, Zhang Y and Liu H: CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS. Mol Med Rep 25: 51, 2022.
APA
Chen, J., Shi, P., Zhang, J., Li, Y., Ma, J., Zhang, Y., & Liu, H. (2022). CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS. Molecular Medicine Reports, 25, 51. https://doi.org/10.3892/mmr.2021.12567
MLA
Chen, J., Shi, P., Zhang, J., Li, Y., Ma, J., Zhang, Y., Liu, H."CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS". Molecular Medicine Reports 25.2 (2022): 51.
Chicago
Chen, J., Shi, P., Zhang, J., Li, Y., Ma, J., Zhang, Y., Liu, H."CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS". Molecular Medicine Reports 25, no. 2 (2022): 51. https://doi.org/10.3892/mmr.2021.12567
Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Shi P, Zhang J, Li Y, Ma J, Zhang Y and Liu H: CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS. Mol Med Rep 25: 51, 2022.
APA
Chen, J., Shi, P., Zhang, J., Li, Y., Ma, J., Zhang, Y., & Liu, H. (2022). CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS. Molecular Medicine Reports, 25, 51. https://doi.org/10.3892/mmr.2021.12567
MLA
Chen, J., Shi, P., Zhang, J., Li, Y., Ma, J., Zhang, Y., Liu, H."CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS". Molecular Medicine Reports 25.2 (2022): 51.
Chicago
Chen, J., Shi, P., Zhang, J., Li, Y., Ma, J., Zhang, Y., Liu, H."CircRNA_0044556 diminishes the sensitivity of triple‑negative breast cancer cells to adriamycin by sponging miR‑145 and regulating NRAS". Molecular Medicine Reports 25, no. 2 (2022): 51. https://doi.org/10.3892/mmr.2021.12567
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