Synergistic antitumor activity of resveratrol and miR-200c in human lung cancer

Bai,Tao; Dong,Dao-Song; Pei,Ling

doi:10.3892/or.2014.3090

Synergistic antitumor activity of resveratrol and miR-200c in human lung cancer

Authors:
- Tao Bai
- Dao-Song Dong
- Ling Pei
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Affiliations: Department of Anaesthesiology, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China
Published online on: March 14, 2014 https://doi.org/10.3892/or.2014.3090
Pages: 2293-2297

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Abstract

microRNAs have emerged as promising molecular factors with potential for clinical applications in cancer diagnosis and therapy. In the present study, we demonstrated that the level of miR-200c in lung cancer tissues was lower than that in normal tissues using real-time PCR. To further investigate the effects of miR-200c expression in lung cancer cells, we upregulated miR-200c levels in H460 cells using transfection. We found that the percentage of apoptotic cells was higher in the cells expressing miR-200c than that in the untransfected cells. Furthermore, the antitumor activities of miR-200c were demonstrated in vivo. Notably, we confirmed that reservatol (RESV) showed stronger antitumor activities in miR-200c-positive cells than in miR-200c-negative cells. Finally, we demonstrated that expression of miR-200c in H460 cells suppressed cell growth by targeting RECK, followed by activation of the JNK signaling pathway and ER stress. Collectively, these data show that miR-200c expression sensitizes H460 cells to RESV and this is likely due to RECK expression.

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1	Ryan BM, Robles AI and Harris CC: Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer. 10:389–402. 2010. View Article : Google Scholar : PubMed/NCBI
2	Kasinski AL and Slack FJ: MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 11:849–864. 2011. View Article : Google Scholar : PubMed/NCBI
3	Edwards JK, Pasqualini R, Arap W and Calin GA: MicroRNAs and ultraconserved genes as diagnostic markers and therapeutic targets in cancer and cardiovascular diseases. J Cardiovasc Transl Res. 3:271–279. 2010. View Article : Google Scholar : PubMed/NCBI
4	Tryndyak VP, Beland FA and Pogribny IP: E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer. 126:2575–2583. 2009.PubMed/NCBI
5	Korpal M, Lee ES, Hu G and Kang Y: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 283:14910–14914. 2008. View Article : Google Scholar : PubMed/NCBI
6	Park SM, Gaur AB, Lengyel E and Peter ME: The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22:894–907. 2008. View Article : Google Scholar : PubMed/NCBI
7	Hurteau GJ, Carlson JA, Roos E and Brock GJ: Stable expression of miR-200c alone is sufficient to regulate TCF8 (ZEB1) and restore E-cadherin expression. Cell Cycle. 8:2064–2069. 2009. View Article : Google Scholar : PubMed/NCBI
8	Hugo H, Ackland ML, Blick T, et al: Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol. 213:374–383. 2007. View Article : Google Scholar : PubMed/NCBI
9	Lee TK, Poon RT, Yuen AP, et al: Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res. 12:5369–5376. 2006. View Article : Google Scholar
10	Miki H, Uehara N, Kimura A, et al: Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol. 40:1020–1028. 2012.PubMed/NCBI
11	Sheths S, Jajoo S, Kaur T, et al: Resveratrolreducesprostate cancer growth and metastasis by inhibiting the Akt/microRNA-21 pathway. PLoS One. 7:e516552012. View Article : Google Scholar : PubMed/NCBI
12	Yin HT, Tian QZ, Guan L, Zhou Y, Huang XE and Zhang H: In vitro and in vivo evaluation of the antitumor efficiency of resveratrol against lung cancer. Asian Pac J Cancer Prev. 14:1703–1706. 2013. View Article : Google Scholar : PubMed/NCBI
13	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
14	Jan CH, Friedman RC, Ruby JG and Bartel DP: Formation, regulation and evolution of Caenorhabditis elegans 3′UTRs. Nature. 469:97–101. 2011. View Article : Google Scholar
15	Tang H, Deng M, Tang Y, et al: miR-200b and miR-200c as prognostic factors and mediators of gastric cancer cell progression. Clin Cancer Res. 19:5602–5612. 2013. View Article : Google Scholar : PubMed/NCBI
16	Ceppi P, Mudduluru G, Kumarswamy R, et al: Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res. 8:1207–1216. 2010. View Article : Google Scholar : PubMed/NCBI
17	Furumoto K, Arii S, Mori A, et al: RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance. Reverse-inducing-cysteine-rich protein with Kazal motifs. Hepatology. 33:189–195. 2001. View Article : Google Scholar
18	Span PN, Sweep CG, Manders P, et al: Matrix metalloproteınase inhibitor reversion-inducing cysteine-rich protein with Kazal motif a prognostic marker for good clinical outcome in human breast carcinoma. Cancer. 97:2710–7215. 2003.
19	Masui T, Doi R, Koshiba T, et al: RECK expression in pancreatic cancer: its correlation with lower invasiveness and better prognosis. Clin Can Res. 9:1779–1784. 2003.PubMed/NCBI
20	Takeuchi T, Hisanaga M, Nagao M, et al: The membrane-anchored matrix metalloproteí nase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer. Clin Cancer Res. 10:5572–5579. 2004.
21	Lei L, Huang Y and Gong W: Inhibition of miR-92b suppresses nonsmall cell lung cancer cells growth and motility by targeting RECK. Mol Cell Biochem. 387:171–176. 2013. View Article : Google Scholar : PubMed/NCBI
22	Chen Y, Tsai YH and Tseng SH: RECK regulated endoplasmic reticulum stress response and enhanced cisplatin-induced cell death in neuroblastoma cells. Surgery. 154:968–979. 2013. View Article : Google Scholar : PubMed/NCBI
23	Moenner M, Pluquet O, Bouchecareilh M, et al: Integrated endoplasmic reticulum stress responses in cancer. Cancer Res. 67:10631–10634. 2007. View Article : Google Scholar : PubMed/NCBI
24	Tamaki N, Hatano E, Taura K, et al: CHOP deficiency attenuates cholestasis-induced liver fibrosis by reduction of hepatocyte injury. Am J Physiol Gastrointest Liver Physiol. 294:G498–G505. 2008. View Article : Google Scholar : PubMed/NCBI