Knockdown of miR‑935 increases paclitaxel sensitivity via regulation of SOX7 in non‑small‑cell lung cancer

Peng,Bing; Li,Chao; Cai,Peng; Yu,Liuyang; Zhao,Bolin; Chen,Guiming

doi:10.3892/mmr.2018.9330

Knockdown of miR‑935 increases paclitaxel sensitivity via regulation of SOX7 in non‑small‑cell lung cancer

Authors:
- Bing Peng
- Chao Li
- Peng Cai
- Liuyang Yu
- Bolin Zhao
- Guiming Chen
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Affiliations: Department of Oncology, The Second People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China
Published online on: July 27, 2018 https://doi.org/10.3892/mmr.2018.9330
Pages: 3397-3402

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Abstract

Sex determining region Y‑box (SOX)7 is a member of the SOX family and is responsible for various developmental processes. As a tumor suppressor, decreased expression of SOX7 has been observed in several cancer types, including non‑small‑cell lung cancer (NSCLC). However, the mechanism underlying SOX7 downregulation and its role in chemoresistance in NSCLC remains poorly understood. In the present study, the inhibition of microRNA (miR)‑935 increased the expression of SOX7 at the mRNA and protein levels in A549 cells. The luciferase reporter assay verified that miR‑935 could directly bind to the 3'untranslated region of SOX7 mRNA to suppress its expression in A549 cells. In addition, the inhibition of miR‑935 enhanced the anticancer effect of paclitaxel, i.e., induced cell growth arrest and apoptosis in A549 cells. It was further observed that the inhibition of miR‑935 decreased the B cell lymphoma (Bcl)‑2 and phosphorylated‑RAC‑α serine/threonine‑protein kinase (AKT) protein levels and increased the Bcl‑2 associated X, apoptosis regulator protein levels, without affecting the AKT levels in the presence of paclitaxel within A549 cells. The findings of the present study validate miR‑935 as a predictor of paclitaxel sensitivity in NSCLC.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Zhu J, Li Q, He JT and Liu GY: Expression of TAK1/TAB1 expression in non-small cell lung carcinoma and adjacent normal tissues and their clinical significance. Int J Clin Exp Pathol. 8:15801–15807. 2015.PubMed/NCBI
3	Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C and Gottesman MM: Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 5:219–234. 2006. View Article : Google Scholar : PubMed/NCBI
4	Gupta N, Hatoum H and Dy GK: First line treatment of advanced non-small-cell lung cancer-specific focus on albumin bound paclitaxel. Int J Nanomedicine. 9:209–221. 2014.PubMed/NCBI
5	Zhou Z, Kennell C, Lee JY, Leung YK and Tarapore P: Calcium phosphate-polymer hybrid nanoparticles for enhanced triple negative breast cancer treatment via co-delivery of paclitaxel and miR-221/222 inhibitors. Nanomedicine. 13:403–410. 2017. View Article : Google Scholar : PubMed/NCBI
6	Fushida S, Kinoshita J, Kaji M, Oyama K, Hirono Y, Tsukada T, Fujimura T and Ohta T: Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: A randomized Phase II trial. Drug Des Devel Ther. 10:2353–2358. 2016. View Article : Google Scholar : PubMed/NCBI
7	Horwitz SB, Cohen D, Rao S, Ringel I, Shen HJ and Yang CP: Taxol: Mechanisms of action and resistance. J Natl Cancer Inst Monogr. 55–61. 1993.PubMed/NCBI
8	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
9	Tufekci KU, Oner MG, Meuwissen RL and Genc S: The role of microRNAs in human diseases. Methods Mol Biol. 1107:33–50. 2014. View Article : Google Scholar : PubMed/NCBI
10	Milagro FI, Miranda J, Portillo MP, Fernandez-Quintela A, Campion J and Martinez JA: High-throughput sequencing of microRNAs in peripheral blood mononuclear cells: Identification of potential weight loss biomarkers. PLoS One. 8:e543192013. View Article : Google Scholar : PubMed/NCBI
11	Genovesi LA, Carter KW, Gottardo NG, Giles KM and Dallas PB: Integrated analysis of miRNA and mRNA expression in childhood medulloblastoma compared with neural stem cells. PLoS One. 6:e239352011. View Article : Google Scholar : PubMed/NCBI
12	Wang C, Feng Z, Jiang K and Zuo X: Upregulation of MicroRNA-935 promotes the malignant behaviors of pancreatic carcinoma PANC-1 cells via targeting inositol polyphosphate 4-phosphatase type I gene (INPP4A). Oncol Res. 25:559–569. 2017. View Article : Google Scholar : PubMed/NCBI
13	Yang M, Cui G, Ding M, Yang W, Liu Y, Dai D and Chen L: miR-935 promotes gastric cancer cell proliferation by targeting SOX7. Biomed Pharmacother. 79:153–158. 2016. View Article : Google Scholar : PubMed/NCBI
14	Liu X, Li J, Yu Z, Li J, Sun R and Kan Q: miR-935 promotes liver cancer cell proliferation and migration by targeting SOX7. Oncol Res. 25:427–435. 2017. View Article : Google Scholar : PubMed/NCBI
15	Bowles J, Schepers G and Koopman P: Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators. Dev Biol. 227:239–255. 2000. View Article : Google Scholar : PubMed/NCBI
16	Stovall DB, Cao P and Sui G: SOX7: From a developmental regulator to an emerging tumor suppressor. Histol Histopathol. 29:439–445. 2014.PubMed/NCBI
17	Cui J, Xi H, Cai A, Bian S, Wei B and Chen L: Decreased expression of Sox7 correlates with the upregulation of the Wnt/β-catenin signaling pathway and the poor survival of gastric cancer patients. Int J Mol Med. 34:197–204. 2014. View Article : Google Scholar : PubMed/NCBI
18	Li B, Ge Z, Song S, Zhang S, Yan H, Huang B and Zhang Y: Decreased expression of SOX7 is correlated with poor prognosis in lung adenocarcinoma patients. Pathol Oncol Res. 18:1039–1045. 2012. View Article : Google Scholar : PubMed/NCBI
19	Guo L, Zhong D, Lau S, Liu X, Dong XY, Sun X, Yang VW, Vertino PM, Moreno CS, Varma V, et al: Sox7 Is an independent checkpoint for beta-catenin function in prostate and colon epithelial cells. Mol Cancer Res. 6:1421–1430. 2008. View Article : Google Scholar : PubMed/NCBI
20	Zheng Z, Liu J, Yang Z, Wu L, Xie H, Jiang C, Lin B, Chen T, Xing C, Liu Z, et al: MicroRNA-452 promotes stem-like cells of hepatocellular carcinoma by inhibiting Sox7 involving Wnt/β-catenin signaling pathway. Oncotarget. 7:28000–28012. 2016. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Reya T and Clevers H: Wnt signalling in stem cells and cancer. Nature. 434:843–850. 2005. View Article : Google Scholar : PubMed/NCBI
23	Baselga J: Targeting the phosphoinositide-3 (PI3) kinase pathway in breast cancer. Oncologist. 16 Suppl 1:S12–S19. 2011. View Article : Google Scholar
24	Danial NN and Korsmeyer SJ: Cell death: Critical control points. Cell. 116:205–219. 2004. View Article : Google Scholar : PubMed/NCBI