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Involvement of miR-143 in cisplatin resistance of gastric cancer cells via targeting IGF1R and BCL2

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Tumor Biology

Abstract

We investigated the possible role of miR-143 in the development of cisplatin resistance in human gastric cancer cell line. miR-143 was detected by quantitative real-time PCR. Cisplatin resistance changes of cells was tested via MTT assay. Target genes of miR-143 were verified by dual-luciferase activity assay. Immunohistochemistry, immunofluorescence staining, Western blot, cell proliferation, and clonogenic and apoptosis assay were used to elucidate the mechanism of miR-143 in cisplatin resistance formation. miR-143 was downregulated in gastric cancer tissues and cell lines. It was also downregulated in cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP), which was concurrent with the upregulation of IGF1R and BCL2, compared with the parental SGC7901 cell line, respectively. Overexpressed miR-143 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity suggested that IGF1R and BCL2 were both target genes of miR-143. Enforced miR-143 reduced its target proteins, inhibited SGC7901/DDP cells proliferation, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Our findings suggested that hsa-miR-143 could modulate cisplatin resistance of human gastric cancer cell line at least in part by targeting IGF1R and BCL2.

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Abbreviations

miRNAs:

MicroRNAs

DDP:

Cisplatin

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

References

  1. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141(1):69–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rabik CA, Dolan ME. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 2007;33:9–23.

    Article  CAS  PubMed  Google Scholar 

  3. Johnstone RW, Ruefli AA, Lowe SW. Apoptosis: a link between cancer genetics and chemotherapy. Cell. 2002;108:153–64.

    Article  CAS  PubMed  Google Scholar 

  4. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.

    Article  CAS  PubMed  Google Scholar 

  5. Hummel R, Hussey DJ, Haier J. MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types. Eur J Cancer. 2010;46(2):298–311.

    Article  CAS  PubMed  Google Scholar 

  6. Takagi T, Iio A, Nakagawa Y, Naoe T, Tanigawa N, Akao Y. Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncol. 2009;77(1):12–21.

    Article  CAS  Google Scholar 

  7. Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, et al. Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther. 2010;17(6):398–408.

    Article  CAS  PubMed  Google Scholar 

  8. Võsa U, Vooder T, Kolde R, Vilo J, Metspalu A, Annilo T. Meta-analysis of microRNA expression in lung cancer. Int J Cancer. 2013;132(12):2884–93.

    Article  PubMed  Google Scholar 

  9. Lui WO, Pourmand N, Patterson BK, Fire A. Patterns of known and novel small RNAs in human cervical cancer. Cancer Res. 2007;67(13):6031–43.

    Article  CAS  PubMed  Google Scholar 

  10. Zhou F, Li S, Meng HM, Qi LQ, Gu L. MicroRNA and histopathological characterization of pure mucinous breast carcinoma. Cancer Biol Med. 2013;10(1):22–7.

    PubMed  PubMed Central  Google Scholar 

  11. Akao Y, Nakagawa Y, Kitade Y, Kinoshita T, Naoe T. Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Sci. 2007;98(12):1914–20.

    Article  CAS  PubMed  Google Scholar 

  12. Yoshino H, Seki N, Itesako T, Chiyomaru T, Nakagawa M, Enokida H. Aberrant expression of microRNAs in bladder cancer. Nat Rev Urol. 2013;10(7):396–404.

    Article  CAS  PubMed  Google Scholar 

  13. Zhao DS, Chen Y, Jiang H, Lu JP, Zhang G, Geng J, et al. Serum miR-210 and miR-30a expressions tend to revert to fetal levels in Chinese adult patients with chronic heart failure. Cardiovasc Pathol. 2013;22(6):444–50.

    Article  CAS  PubMed  Google Scholar 

  14. Zhu W, Shan X, Wang TS, Shu YQ, Liu P. miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int J Cancer. 2010;127(11):2520–9.

    Article  CAS  PubMed  Google Scholar 

  15. Ge J, Chen Z, Wu S, Chen J, Li X, Li J, et al. Expression levels of insulin-like growth factor-1 and multidrug resistance-associated protein-1 indicate poor prognosis in patients with gastric cancer. Digestion. 2009;80(3):148–58.

    Article  CAS  PubMed  Google Scholar 

  16. Hopkins A, Crowe PJ, Yang JL. Effect of type 1 insulin-like growth factor receptor targeted therapy on chemotherapy in human cancer and the mechanisms involved. J Cancer Res Clin Oncol. 2010;136(5):639–50.

    Article  CAS  PubMed  Google Scholar 

  17. Murayama T, Inokuchi M, Takagi Y, Yamada H, Kojima K, Kumagai J, et al. Relation between outcomes and localisation of p-mTOR expression in gastric cancer. Br J Cancer. 2009;100(5):782–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yu G, Wang J, Chen Y, Wang X, Pan J, Li G, et al. Overexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of Chinese patients with gastric cancer. Clin Cancer Res. 2009;15(5):1821–9.

    Article  CAS  PubMed  Google Scholar 

  19. Tanida S, Mizoshita T, Ozeki K, Tsukamoto H, Kamiya T, Kataoka H, et al. Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity: potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment. Int J Surg Oncol. 2012;2012, 862879.

    PubMed  PubMed Central  Google Scholar 

  20. Eckstein N, Servan K, Hildebrandt B, Politz A, von Jonquières G, Wolf-Kummeth S, et al. Hyperactivation of the insulin-like growth factor receptor I signaling pathway is an essential event for cisplatin resistance of ovarian cancer cells. Cancer Res. 2009;69(7):2996–3003.

    Article  CAS  PubMed  Google Scholar 

  21. Liu SG, Qin XG, Zhao BS, Qi B, Yao WJ, Wang TY, et al. Differential expression of miRNAs in esophageal cancer tissue. Oncol Lett. 2013;5(5):1639–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Walter BA, Valera VA, Pinto PA, Merino MJ. Comprehensive microRNA profiling of prostate cancer. J Cancer. 2013;4(5):350–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors are grateful to the fund support by the National Natural Science Foundation of China (Grant number 81201705) and the Natural Science Foundation of Jiangsu Province (Grant number BK2012442).

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Correspondence to Wei Zhu or Yongqian Shu.

Additional information

Ming Zhuang and Qin Shi contributed equally to this work.

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Zhuang, M., Shi, Q., Zhang, X. et al. Involvement of miR-143 in cisplatin resistance of gastric cancer cells via targeting IGF1R and BCL2. Tumor Biol. 36, 2737–2745 (2015). https://doi.org/10.1007/s13277-014-2898-5

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  • DOI: https://doi.org/10.1007/s13277-014-2898-5

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