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Molecular Medicine Reports
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October-2015 Volume 12 Issue 4

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Article

MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues

  • Authors:
    • Li Wang
    • Yan Ming Wang
    • Song Xu
    • Wei Guo Wang
    • Yang Chen
    • Jing Yu Mao
    • Bo Le Tian
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
  • Pages: 5274-5280
    |
    Published online on: July 1, 2015
       https://doi.org/10.3892/mmr.2015.4012
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Abstract

Non-coding microRNAs (miRNAs), involved in post-transcriptional control, are widely involved in the mechanism of cellular resistance to antitumor chemotherapy. Ectopic expression of one of these miRNAs, miRNA‑215 (miR‑215), leads to chemoresistance by directly targeting dihydrofolate reductase (DHFR) and thymidylate synthase (TS), which are two of the most important targets of chemotherapeutic agents. This indicates the possible upregulation of endogenous miR‑215 in the process of chemoresistance by interfering with important transcripts. In the present study, the upregulation of miR‑215 was examined in hepatocellular carcinoma (HCC) subcell lines, Adriamycin (ADM)‑resistant HepG2 (HepG2/AR), Hep3B (Hep3B/AR) cell lines, and in ADM‑treated patients with HCC. Upregulated miR‑215 directly targeted DHFR and TS mRNA and reduced their protein expression levels, without altering mRNA levels. The ectopic expression of miR‑215 anti‑sense oligo‑nucleotides in HepG2/AR and Hep3B/AR cells enhanced chemosensitivity, whereas the expression of the miR‑215 mimics led to chemoresistance. Notably, the upregulation of miR‑215 indirectly increased the protein levels of P53 and P21 levels in the HepG2 cells, which contain functional P53, which is expected to result in the inhibition of proliferation and colony formation. Taken together, the present study demonstrated that the upregulation of miR‑215 resulting from ADM treatment in HCC cells leads to the development of insensitivity to ADM and worsens the prognosis of patients with HCC exhibiting mutated P53.
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Copy and paste a formatted citation
Spandidos Publications style
Wang L, Wang YM, Xu S, Wang WG, Chen Y, Mao JY and Tian BL: MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues. Mol Med Rep 12: 5274-5280, 2015.
APA
Wang, L., Wang, Y.M., Xu, S., Wang, W.G., Chen, Y., Mao, J.Y., & Tian, B.L. (2015). MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues. Molecular Medicine Reports, 12, 5274-5280. https://doi.org/10.3892/mmr.2015.4012
MLA
Wang, L., Wang, Y. M., Xu, S., Wang, W. G., Chen, Y., Mao, J. Y., Tian, B. L."MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues". Molecular Medicine Reports 12.4 (2015): 5274-5280.
Chicago
Wang, L., Wang, Y. M., Xu, S., Wang, W. G., Chen, Y., Mao, J. Y., Tian, B. L."MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues". Molecular Medicine Reports 12, no. 4 (2015): 5274-5280. https://doi.org/10.3892/mmr.2015.4012
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Wang YM, Xu S, Wang WG, Chen Y, Mao JY and Tian BL: MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues. Mol Med Rep 12: 5274-5280, 2015.
APA
Wang, L., Wang, Y.M., Xu, S., Wang, W.G., Chen, Y., Mao, J.Y., & Tian, B.L. (2015). MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues. Molecular Medicine Reports, 12, 5274-5280. https://doi.org/10.3892/mmr.2015.4012
MLA
Wang, L., Wang, Y. M., Xu, S., Wang, W. G., Chen, Y., Mao, J. Y., Tian, B. L."MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues". Molecular Medicine Reports 12.4 (2015): 5274-5280.
Chicago
Wang, L., Wang, Y. M., Xu, S., Wang, W. G., Chen, Y., Mao, J. Y., Tian, B. L."MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues". Molecular Medicine Reports 12, no. 4 (2015): 5274-5280. https://doi.org/10.3892/mmr.2015.4012
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