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miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2

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Abstract

MicroRNAs (miRNAs) are short non-coding RNA molecules, which posttranscriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Here, we investigated the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines. We found that miR-497 was downregulated in both multidrug-resistant human gastric cancer cell line SGC7901/vincristine (VCR) and multidrug-resistant human lung cancer cell line A549/cisplatin (CDDP) and the downregulation of miR-497 was concurrent with the upregulation of BCL2 protein, compared with the parental SGC7901 and A549 cell lines, respectively. In vitro drug sensitivity assay demonstrated that overexpression of miR-497 sensitized SGC7901/VCR and A549/CDDP cells to anticancer drugs, respectively. The luciferase activity of BCL2 3′-untranslated region-based reporter constructed in SGC7901/VCR and A549/CDDP cells suggested that BCL2 was the direct target gene of miR-497. Enforced miR-497 expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively. Taken together, our findings first suggested that has-miR-497 could play a role in both gastric and lung cancer cell lines at least in part by modulation of apoptosis via targeting BCL2.

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Abbreviations

miRNAs:

MicroRNAs.

MDR:

Multidrug resistance.

VCR:

Vincristine.

CDDP:

Cisplatin

5-Fu:

5-fluorouracil

VP-16:

Etoposide

ADR:

Adriamycin

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Acknowledgments

The authors are grateful to the fund support by the National Natural Science Foundation of China (Grant number: 30840095) and the Cancer Center of Nanjing Medical University (Grant number: 08ZLKF02).

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Authors and Affiliations

  1. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, People’s Republic of China

    Wei Zhu, Tongshan Wang, Jian Wang, Yongqian Shu & Ping Liu

  2. Cancer Center of Nanjing Medical University, 140 Hanzhong Road, 210029, Nanjing, People’s Republic of China

    Binghua Jiang, Yongqian Shu & Ping Liu

  3. Department of Haematology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, People’s Republic of China

    DanXia Zhu

  4. Department of Microbiology and Immunology, Nanjing Medical University, 140 Hanzhong Road, 210029, Nanjing, People’s Republic of China

    Shiqiang Lu

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  1. Wei Zhu
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Corresponding author

Correspondence to Ping Liu.

Additional information

Wei Zhu and DanXia Zhu equally contributed to this study.

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Zhu, W., Zhu, D., Lu, S. et al. miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med Oncol 29, 384–391 (2012). https://doi.org/10.1007/s12032-010-9797-4

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  • DOI: https://doi.org/10.1007/s12032-010-9797-4

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