Downregulation of microRNA‑301a inhibited proliferation, migration and invasion of non‑small cell lung cancer by directly targeting DLC1

Wu,Zhuyu; Li,Yaojun; Zhang,Guojun

doi:10.3892/ol.2017.6990

Downregulation of microRNA‑301a inhibited proliferation, migration and invasion of non‑small cell lung cancer by directly targeting DLC1

Authors:
- Zhuyu Wu
- Yaojun Li
- Guojun Zhang
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China, Department of Respiratory Medicine, Luohe Central Hospital, Luohe, Henan 462000, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/ol.2017.6990
Pages: 6017-6023
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increasing evidence has indicated that the abnormal expression of microRNAs contributes to tumorigenesis and tumor development. Understanding the roles of microRNAs in non‑small cell lung cancer (NSCLC) might provide valuable information for therapeutic strategies in the therapy for patients with NSCLC. In the present study, significant upregulation of microRNA (miR)‑301a was observed in NSCLC tissues and cell lines compared with normal adjacent tissues and a normal human bronchial epithelial cell line. The inhibition of miR‑301a suppressed proliferation, migration and invasion of NSCLC cells. Functional analyses indicated that DLC1 was a direct target of miR‑301a in NSCLC. Inhibiting miR‑301a expression decreased DLC1 expression at mRNA and protein levels. Moreover, DLC1 knockdown partially reversed the inhibition of proliferation, migration and invasion induced by miR‑301a knockdown in NSCLC cells. Therefore, these findings may provide novel insights into the molecular mechanisms of miR‑301a in proliferation, migration and invasion of NSCLC cells. The findings also indicated that miR‑301a may act as a novel potential therapeutic target for patients with NSCLC.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
2	Spira A and Ettinger DS: Multidisciplinary management of lung cancer. N Engl J Med. 350:379–392. 2004. View Article : Google Scholar : PubMed/NCBI
3	Yang L, Parkin DM, Li L and Chen Y: Time trends in cancer mortality in China: 1987–1999. Int J Cancer. 106:771–783. 2003. View Article : Google Scholar : PubMed/NCBI
4	Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, Olak J, Stover D, Strawn JR, Turrisi AT, et al: American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: Update 2003. J Clin Oncol. 22:330–353. 2004. View Article : Google Scholar : PubMed/NCBI
5	Yilmaz A, Damadoglu E, Salturk C, Okur E, Tuncer LY and Halezeroglu S: Delays in the diagnosis and treatment of primary lung cancer: Are longer delays associated with advanced pathological stage? Ups J Med Sci. 113:287–296. 2008. View Article : Google Scholar : PubMed/NCBI
6	Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L and Kunkler I: EUROCARE-4 Working Group: Recent cancer survival in Europe: A 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol. 8:784–796. 2007. View Article : Google Scholar : PubMed/NCBI
7	Somaiah N and Simon GR: Molecular targeted agents and biologic therapies for non-small cell lung cancer. J Thorac Oncol. 5 12 Suppl 6:S434–S454. 2010. View Article : Google Scholar : PubMed/NCBI
8	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
9	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
10	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
11	Donadeu FX, Schauer SN and Sontakke SD: Involvement of miRNAs in ovarian follicular and luteal development. J Endocrinol. 215:323–334. 2012. View Article : Google Scholar : PubMed/NCBI
12	Liwak U, Faye MD and Holcik M: Translation control in apoptosis. Exp Oncol. 34:218–230. 2012.PubMed/NCBI
13	Rutnam ZJ and Yang BB: The involvement of microRNAs in malignant transformation. Histol Histopathol. 27:1263–1270. 2012.PubMed/NCBI
14	Rothschild SI: Epigenetic therapy in lung cancer-role of microRNAs. Front Oncol. 3:1582013. View Article : Google Scholar : PubMed/NCBI
15	Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI
16	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
17	Yuan BZ, Jefferson AM, Baldwin KT, Thorgeirsson SS, Popescu NC and Reynolds SH: DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas. Oncogene. 23:1405–1411. 2004. View Article : Google Scholar : PubMed/NCBI
18	Feng H, Zhang Z, Wang X and Liu D: Identification of DLC-1 expression and methylation status in patients with non-small-cell lung cancer. Mol Clin Oncol. 4:249–254. 2016. View Article : Google Scholar : PubMed/NCBI
19	Healy KD, Hodgson L, Kim TY, Shutes A, Maddileti S, Juliano RL, Hahn KM, Harden TK, Bang YJ and Der CJ: DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms. Mol Carcinog. 47:326–337. 2008. View Article : Google Scholar : PubMed/NCBI
20	Liu XH, Liu ZL, Sun M, Liu J, Wang ZX and De W: The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer. 13:4642013. View Article : Google Scholar : PubMed/NCBI
21	Chen X, Chen S, Hang W, Huang H and Ma H: MiR-95 induces proliferation and chemo- or radioresistance through directly targeting sorting nexin1 (SNX1) in non-small cell lung cancer. Biomed Pharmacother. 68:589–595. 2014. View Article : Google Scholar : PubMed/NCBI
22	Zhang Y, Zhao Y, Sun S, Liu Z, Zhang Y and Jiao S: Overexpression of MicroRNA-221 is associated with poor prognosis in non-small cell lung cancer patients. Tumour Biol. 37:10155–10160. 2016. View Article : Google Scholar : PubMed/NCBI
23	Chen X, Gong J, Zeng H, Chen N, Huang R, Huang Y, Nie L, Xu M, Xia J, Zhao F, et al: MicroRNA145 targets BNIP3 and suppresses prostate cancer progression. Cancer Res. 70:2728–2738. 2010. View Article : Google Scholar : PubMed/NCBI
24	Wu D, Zhou Y, Pan H, Zhou J, Fan Y and Qu P: microRNA-99a inhibiting cell proliferation, migration and invasion by targeting fibroblast growth factor receptor 3 in bladder cancer. Oncol Lett. 7:1219–1224. 2014.PubMed/NCBI
25	Xu T, Liu X, Han L, Shen H, Liu L and Shu Y: Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer. Clin Transl Oncol. 16:469–475. 2014. View Article : Google Scholar : PubMed/NCBI
26	Bai Y, Wang YL, Yao WJ, Guo L, Xi HF, Li SY and Zhao BS: Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival. Int J Clin Exp Pathol. 8:824–829. 2015.PubMed/NCBI
27	Kawano M, Tanaka K, Itonaga I, Iwasaki T and Tsumura H: MicroRNA-301a promotes cell proliferation via PTEN targeting in Ewing's sarcoma cells. Int J Oncol. 48:1531–1540. 2016. View Article : Google Scholar : PubMed/NCBI
28	Lu Y, Gao W, Zhang C, Wen S, Huangfu H, Kang J and Wang B: Hsa-miR-301a-3p acts as an oncogene in laryngeal squamous cell carcinoma via target regulation of Smad4. J Cancer. 6:1260–1275. 2015. View Article : Google Scholar : PubMed/NCBI
29	Xia X, Zhang K, Cen G, Jiang T, Cao J, Huang K, Huang C, Zhao Q and Qiu Z: MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4. Oncotarget. 6:21046–21063. 2015. View Article : Google Scholar : PubMed/NCBI
30	Fang Y, Sun B, Xiang J and Chen Z: MiR-301a promotes colorectal cancer cell growth and invasion by directly targeting SOCS6. Cell Physiol Biochem. 35:227–236. 2015. View Article : Google Scholar : PubMed/NCBI
31	Xu XD, He XJ, Tao HQ, Zhang W, Wang YY, Ye ZY and Zhao ZS: Abnormal expression of miR-301a in gastric cancer associated with progression and poor prognosis. J Surg Oncol. 108:197–202. 2013. View Article : Google Scholar : PubMed/NCBI
32	Zhou P, Jiang W, Wu L, Chang R, Wu K and Wang Z: miR-301a is a candidate oncogene that targets the homeobox gene Gax in human hepatocellular carcinoma. Dig Dis Sci. 57:1171–1180. 2012. View Article : Google Scholar : PubMed/NCBI
33	Yu H, Li H, Qian H, Jiao X, Zhu X, Jiang X, Dai G and Huang J: Upregulation of miR-301a correlates with poor prognosis in triple-negative breast cancer. Med Oncol. 31:2832014. View Article : Google Scholar : PubMed/NCBI
34	Ma F, Zhang J, Zhong L, Wang L, Liu Y, Wang Y, Peng L and Guo B: Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting PTEN and activating Wnt/β-catenin signaling. Gene. 535:191–197. 2014. View Article : Google Scholar : PubMed/NCBI
35	Chen Z, Chen LY, Dai HY, Wang P, Gao S and Wang K: miR-301a promotes pancreatic cancer cell proliferation by directly inhibiting Bim expression. J Cell Biochem. 113:3229–3235. 2012. View Article : Google Scholar : PubMed/NCBI
36	Wang M, Li C, Yu B, Su L, Li J, Ju J, Yu Y, Gu Q, Zhu Z and Liu B: Overexpressed miR-301a promotes cell proliferation and invasion by targeting RUNX3 in gastric cancer. J Gastroenterol. 48:1023–1033. 2013. View Article : Google Scholar : PubMed/NCBI
37	Zhang W, Zhang T, Jin R, Zhao H, Hu J, Feng B, Zang L, Zheng M and Wang M: MicroRNA-301a promotes migration and invasion by targeting TGFBR2 in human colorectal cancer. J Exp Clin Cancer Res. 33:1132014. View Article : Google Scholar : PubMed/NCBI
38	Zhang Y, Duan G and Feng S: MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1. Biochem Biophys Res Commun. 459:367–373. 2015. View Article : Google Scholar : PubMed/NCBI