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
December-2017 Volume 16 Issue 6

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
December-2017 Volume 16 Issue 6

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

miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma

  • Authors:
    • Wei Yuan
    • Du Wang
    • Yang Liu
    • Dongdong Tian
    • Yang Wang
    • Ranxi Zhang
    • Liangjun Yin
    • Zhongliang Deng
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China, Department of Orthopedics, Wuhan Hospital No. 3 and Tongren Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
    Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 8627-8634
    |
    Published online on: October 4, 2017
       https://doi.org/10.3892/mmr.2017.7709
  • 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

Tumorigenesis is a multistep process involving various cell growth‑associated factors. Accumulated evidence indicates that the disordered regulation of microRNAs (miRNAs) contributes to tumorigenesis. However, the detailed mechanism underlying the involvement of miRNAs in oncogenesis remains to be fully elucidated. In the present study, the repressed expression of microRNA (miR)‑494 was identified in 18 patients with osteosarcoma (OS) and OS cell lines, compared with corresponding controls. To determine whether deregulated miR‑494 exerts tumor‑suppressive effects in the development of OS, the effects of miR‑494 on cell proliferation and metastasis were evaluated. It was found that the restoration of miR‑494 in MG‑63 and U2OS cells led to inhibited cell proliferation and attenuated migratory propensity in vitro, determined through analysis using MTT, colony formation and Transwell assays. In addition, overexpression of miR‑494 markedly suppressed the tumor volume and weight in vivo. In accordance, the ectopic expression of miR‑494 induced cell cycle arrest at the G1/S phase in OS cells. Bioinformatics analysis and luciferase reporter assays were performed to investigate the potential regulatory role of miR‑494, the results of which indicated that miR‑494 directly targeted cyclin‑dependent kinase 6 (CDK6). Of note, the data obtained through reverse transcription‑quantitative polymerase chain reaction and western blot analyses suggested that the elevated expression of miR‑494 resulted in reduced mRNA and protein expression levels of CDK6. Taken together, these findings indicated that the miR‑494/CDK6 axis has a significant tumor‑suppressive effect on OS, and maybe a diagnostic and therapeutic target for the treatment of OS.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Luetke A, Meyers PA, Lewis I and Juergens H: Osteosarcoma treatment-where do we stand? A state of the art review. Cancer Treat Rev. 40:523–532. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Benjamin RS: Osteosarcoma: Better treatment through better trial design. Lancet Oncol. 16:12–13. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Xiong Y, Wu S, Du Q, Wang A and Wang Z: Integrated analysis of gene expression and genomic aberration data in osteosarcoma (OS). Cancer Gene Ther. 22:524–529. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Lulla RR, Costa FF, Bischof JM, Chou PM, de F, Bonaldo M, Vanin EF and Soares MB: Identification of differentially expressed micrornas in osteosarcoma. Sarcoma. 2011:7326902011. View Article : Google Scholar : PubMed/NCBI

5 

Marina N, Gebhardt M, Teot L and Gorlick R: Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 9:422–441. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Romano F, Garancini M and Uggeri F, Degrate L, Nespoli L, Gianotti L, Nespoli A and Uggeri F: Surgical treatment of liver metastases of gastric cancer: State of the art. World J Surg Oncol. 10:1572012. View Article : Google Scholar : PubMed/NCBI

7 

Olaru AV, Ghiaur G, Yamanaka S, Luvsanjav D, An F, Popescu I, Alexandrescu S, Allen S, Pawlik TM, Torbenson M, et al: MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint. Hepatology. 54:2089–2098. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Hong KJ, Wu DC, Cheng KH, Chen LT and Hung WC: RECK inhibits stemness gene expression and tumorigenicity of gastric cancer cells by suppressing ADAM-mediated Notch1 activation. J Cell Physiol. 229:191–201. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Ma YB, Li GX, Hu JX, Liu X and Shi BM: Correlation of miR-494 expression with tumor progression and patient survival in pancreatic cancer. Genet Mol Res. 14:18153–18159. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Tian C, Zheng G, Zhuang H, Li X, Hu D, Zhu L, Wang T, You MJ and Zhang Y: MicroRNA-494 activation suppresses bone marrow stromal cell-mediated drug resistance in acute myeloid leukemia cells. J Cell Physiol. 232:1387–1395. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Lim L, Balakrishnan A, Huskey N, Jones KD, Jodari M, Ng R, Song G, Riordan J, Anderton B, Cheung ST, et al: MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology. 59:202–215. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Zhao X, Zhou Y, Chen YU and Yu F: miR-494 inhibits ovarian cancer cell proliferation and promotes apoptosis by targeting FGFR2. OncolLett. 11:4245–4251. 2016.

13 

Yuan J, Wang K and Xi M: miR-494 inhibits epithelial ovarian cancer growth by targeting c-Myc. Med Sci Monit. 22:617–624. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Tian C, Zheng G, Zhuang H, Li X, Hu D, Zhu L, Wang T, You MJ and Zhang Y: MicroRNA-494 activation suppresses bone marrow stromal cell-mediated drug resistance inacute myeloid leukemia cells. J Cell Physiol. 232:1387–1395. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, Li Y, Carpenter EL, Attiyeh EF, Diskin SJ, et al: Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 19:6173–6182. 2013. 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 

Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M and Rajewsky N: Combinatorial microRNA target predictions. Nat Genet. 37:495–500. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:2015. View Article : Google Scholar

19 

Griffiths-Jones S, Saini HK, van Dongen S and Enright AJ: miRBase: Tools for microRNA genomics. Nucleic Acids Res. 36(Database issue): D154–D158. 2008.PubMed/NCBI

20 

Liu S and Feng P: miR-203 determines poor outcome and suppresses tumor growth by targeting tbk1 in osteosarcoma. Cell Physiol Biochem. 37:1956–1966. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Vanas V, Haigl B, Stockhammer V and Sutterlüty-Fall H: MicroRNA-21 increases proliferation and cisplatin sensitivity of osteosarcoma-derived cells. PLoS One. 11:e01610232016. View Article : Google Scholar : PubMed/NCBI

22 

Yao J, Qin L, Miao S, Wang X and Wu X: Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1. Oncol Lett. 12:1840–1848. 2016.PubMed/NCBI

23 

Li Y, Liu J, Liu ZZ and Wei WB: MicroRNA-145 inhibits tumour growth and metastasis in osteosarcoma by targeting cyclin-dependent kinase, CDK6. Eur Rev Med Pharmacol Sci. 20:5117–5125. 2016.PubMed/NCBI

24 

Roscigno G, Puoti I, Giordano I, Donnarumma E, Russo V, Affinito A, Adamo A, Quintavalle C, Todaro M, Vivanco MD and Condorelli G: miR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer. Oncotarget. 8:19507–19521. 2017.PubMed/NCBI

25 

Zhu D, Tu M, Zeng B, Cai L, Zheng W, Su Z and Yu Z: Up-regulation of miR-497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl-2. Cancer Med. 6:452–462. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Shyamasundar S, Lim JP and Bay BH: miR-93 inhibits the invasive potential of triple-negative breast cancer cells in vitro via protein kinase WNK1. Int J Oncol. 49:2629–2636. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Huang S, Li X and Zhu H: MicroRNA-152 targets phosphatase and tensin homolog to inhibit apoptosis and promote cell migration of nasopharyngeal carcinoma cells. Med Sci Monit. 22:4330–4337. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Qu Y, Pan S, Kang M, Dong R and Zhao J: MicroRNA-150 functions as a tumor suppressor in osteosarcomaby targeting IGF2BP1. Tumour Biol. 37:5275–5284. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Jiang X, Li X, Wu F, Gao H, Wang G, Zheng H, Wang H, Li J and Chen C: Overexpression of miR-92a promotes the tumor growth of osteosarcoma by suppressing F-box and WD repeat-containing protein 7. Gene. 606:10–16. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Shen PF, Chen XQ, Liao YC, Chen N, Zhou Q, Wei Q, Li X, Wang J and Zeng H: MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion and migration of prostate cancer. Prostate. 74:756–767. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Zhao XQ, Liang TJ and Fu JW: miR-494 inhibits invasion and proliferation of gastric cancer by targeting IGF-1R. Eur Rev Med Pharmacol Sci. 20:3818–3824. 2016.PubMed/NCBI

32 

Handschick K, Beuerlein K, Jurida L, Bartkuhn M, Müller H, Soelch J, Weber A, Dittrich-Breiholz O, Schneider H, Scharfe M, et al: Cyclin-dependent kinase 6 is a chromatin-bound cofactor for NF-κB-dependent gene expression. Mol Cell. 53:193–208. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Wiedemeyer WR, Dunn IF, Quayle SN, Zhang J, Chheda MG, Dunn GP, Zhuang L, Rosenbluh J, Chen S, Xiao Y, et al: Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM. Proc Natl Acad Sci USA. 107:pp. 11501–11506. 2010; View Article : Google Scholar : PubMed/NCBI

34 

Tsai JW, Li CF, Kao YC, Wang JW, Fang FM, Wang YH, Wu WR, Wu LC, Hsing CH, Li SH, et al: Recurrent amplification at 7q21.2 Targets CDK6 gene in primary myxofibrosarcomas and identifies CDK6 overexpression as an independent adverse prognosticator. Ann Surg Oncol. 19:2716–2725. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yuan W, Wang D, Liu Y, Tian D, Wang Y, Zhang R, Yin L and Deng Z: miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma. Mol Med Rep 16: 8627-8634, 2017.
APA
Yuan, W., Wang, D., Liu, Y., Tian, D., Wang, Y., Zhang, R. ... Deng, Z. (2017). miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma. Molecular Medicine Reports, 16, 8627-8634. https://doi.org/10.3892/mmr.2017.7709
MLA
Yuan, W., Wang, D., Liu, Y., Tian, D., Wang, Y., Zhang, R., Yin, L., Deng, Z."miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma". Molecular Medicine Reports 16.6 (2017): 8627-8634.
Chicago
Yuan, W., Wang, D., Liu, Y., Tian, D., Wang, Y., Zhang, R., Yin, L., Deng, Z."miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma". Molecular Medicine Reports 16, no. 6 (2017): 8627-8634. https://doi.org/10.3892/mmr.2017.7709
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan W, Wang D, Liu Y, Tian D, Wang Y, Zhang R, Yin L and Deng Z: miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma. Mol Med Rep 16: 8627-8634, 2017.
APA
Yuan, W., Wang, D., Liu, Y., Tian, D., Wang, Y., Zhang, R. ... Deng, Z. (2017). miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma. Molecular Medicine Reports, 16, 8627-8634. https://doi.org/10.3892/mmr.2017.7709
MLA
Yuan, W., Wang, D., Liu, Y., Tian, D., Wang, Y., Zhang, R., Yin, L., Deng, Z."miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma". Molecular Medicine Reports 16.6 (2017): 8627-8634.
Chicago
Yuan, W., Wang, D., Liu, Y., Tian, D., Wang, Y., Zhang, R., Yin, L., Deng, Z."miR‑494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma". Molecular Medicine Reports 16, no. 6 (2017): 8627-8634. https://doi.org/10.3892/mmr.2017.7709
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