Abstract
Previous studies have reported that microRNA-30e (miR-30e) is dysregulated in multiple human cancers. However, the expression, functions and molecular mechanism of miR-30e in NSCLC remain unknown. In this study, we found that miR-30e was expressed at a low level in NSCLC tissues and cell lines. In NSCLC cell lines, enforced expression of miR-30e could inhibit cell proliferation and invasion in vitro. In addition, miR-30e negatively regulated SOX9 expression through directly binding to the 3′UTR of SOX9, and an inverse correlation was found between miR-30e and SOX9 mRNA expression in NSCLC tissues. Moreover, knockdown of SOX9 led to decreased proliferation and invasion of NSCLC cells. Taken together, miR-30e acts as a tumor suppressor in NSCLC, and inhibits cell proliferation and invasion possibly by directly targeting SOX9. These findings might provide novel therapeutic targets for NSCLC.
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Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.
Fiteni F, Anota A, Westeel V, Bonnetain F. Methodology of health-related quality of life analysis in phaseIII advanced non-small-cell lung cancer clinical trials: a critical review. BMC Cancer. 2016;16:122.
Li Z, Song Y, Liu L, et al. miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation. Cell Death Differ. 2017;24(7):1205–13.
Mao M, Wu Z, Chen J. MicroRNA-187-5p suppresses cancer cell progression in non small cell lung cancer(NSCLC) through down-regulation of CYP1B1. Biochem Biophys Res Commun. 2016;478:649–55.
Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005;6:376–85.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.
Aigner A. MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl). 2011;89:445–57.
Rottiers V, Naar AM. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 2012;13:239–50.
Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 2010;42:1273–81.
Xia H, Li Y, Lv X. MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated PI3K/AKT pathway in human non-small lung cancer. Int J Oncol. 2016;49(4):1325–33.
Lu C, Xie Z, Peng Q. MiRNA-107 enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bcl-w in non small cell lung cancer. Am J Cancer Res 2017,7(9):1863.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.
Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010;9:775–89.
Lin Z, Li JW, Wang Y, et al. Abnormal miRNA-30e expression is associated with breast cancer progression. Clin Lab. 2016;62:121–8.
Kwak S, Kim B, Ahn H, et al. Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B. Febs J. 2015;282(8):1512–25.
Hershkovitzrokah O, Modai S, Pasmanikchor M, et al. MiR-30e induces apoptosis and sensitizes K562 cells to imatinib treatment via regulation of the BCR-ABL protein. Cancer Lett. 2015;356(2):597–605.
Wang X, Ju Y, Zhou MI, Liu X, Zhou C. Upregulation of SOX9 promotes cell proliferation, migration and invasion in lung adenocarcinoma. Oncol Lett. 2015;10:990–4.
Wang X, Liu Y, Liu X, Yang J, Teng G, Zhang L, Zhou C. MiR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma. Oncol Rep. 2016;35:3115–21.
Zhang YJ, Xu F, Zhang YJ, Li HB, Han JC, Li L. miR-206 inhibits non small cell lung cancer cell proliferation and invasion by targeting SOX9. Int J Clin Exp Med. 2015;8:9107–13.
Zhu D, Chen H, Yang X, Chen W, Wang L, Xu J, Yu L. miR-32 functions as a tumor suppressor and directly targets SOX9 in human non-small cell lung cancer. Onco Targets Ther. 2015;8:1773–83.
Wang H, Leav I, Ibaragi S, Wegner M, Hu GF, Lu ML, Balk SP, Yuan X. SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion. Cancer Res. 2008;68:1625–30.
Muller P, Crofts JD, Newman BS, Bridgewater LC, Lin CY, Gustafsson JA, Strom A. SOX9 mediates the retinoic acid-induced HES-1 gene expression in human breast cancer cells. Breast Cancer Res Treat. 2010;120:317–26.
Bruun J, Kolberg M, Nesland JM, Svindland A, Nesbakken A, Lothe RA. Prognostic significance of beta-catenin, e-cadherin, and SOX9 in colorectal cancer: results from a large population-representative series. Front Oncol. 2014;4:118.
Jiang SS, Fang WT, Hou YH, Huang SF, Yen BL, Chang JL, Li SM, Liu HP, Liu YL, Huang CT, Li YW, Jang TH, Chan SH, Yang SJ, Hsiung CA, Wu CW, Wang LH. Chang IS. Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. Clin Cancer Res. 2010;16:4363–73.
Zhou CH, Ye LP, Ye SX, Li Y, Zhang XY, Xu XY, Gong LY. Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival. J Exp Clin Cancer Res. 2012;31:18.
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This work was supported by a grant from the National Nature Science Foundation of China (181774078, 81773453, 81803886), National Nature Science Foundation of Liaoning Province, China (201602227, 20170540300).
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Cui, Y., Zhao, L., Zhao, S. et al. MicroRNA-30e inhibits proliferation and invasion of non-small cell lung cancer via targeting SOX9. Human Cell 32, 326–333 (2019). https://doi.org/10.1007/s13577-018-0223-0
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DOI: https://doi.org/10.1007/s13577-018-0223-0