MicroRNA‑361‑5p suppresses cancer progression by targeting signal transducer and activator of transcription 6 in non‑small cell lung cancer

Ma,Yuefeng; Bao,Chuanen; Kong,Ranran; Xing,Xin; Zhang,Yaya; Li,Shaomin; Zhang,Wei; Jiang,Jiantao; Zhang,Jin; Qiao,Zhe; Zhang,Danjie; Ma,Zhenchuan; Sun,Liangzhang; Zhou,Bin

doi:10.3892/mmr.2015.4411

MicroRNA‑361‑5p suppresses cancer progression by targeting signal transducer and activator of transcription 6 in non‑small cell lung cancer

Authors:
- Yuefeng Ma
- Chuanen Bao
- Ranran Kong
- Xin Xing
- Yaya Zhang
- Shaomin Li
- Wei Zhang
- Jiantao Jiang
- Jin Zhang
- Zhe Qiao
- Danjie Zhang
- Zhenchuan Ma
- Liangzhang Sun
- Bin Zhou
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Affiliations: Department of Thoracic Surgery, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Thoracic and Cardiovascular Surgery, The 174th Hospital of The Chinese People's Liberation Army, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian 710049, P.R. China, Department of Health Care for Cadres, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Oncology, The 174th Hospital of The Chinese People's Liberation Army, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian 710049, P.R. China
Published online on: October 1, 2015 https://doi.org/10.3892/mmr.2015.4411
Pages: 7367-7373
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The incidence of non‑small cell lung cancer (NSCLC) has significantly increased in China, while the prognosis of affected patients is poor. The pathogenesis of NSCLC is thought to be regulated by microRNAs (miRs). The present study used a miR array in order to determine the expression of miR‑361‑5p, which was significantly lower in NSCLC tissues compared with that in adjacent tissues, indicating a crucial role of miR‑361‑5p during the progression of NSCLC. Furthermore, the effects of transfection-induced upregulation of miR‑361‑5p on the NSCLC cell line H23 were assessed. Overexpression of miR‑361‑5p inhibited the proliferation and colony formation ability of H23 cells. In addition, apoptosis of H23 cells was induced by upregulation of miR‑361‑5p. Furthermore, signal transducer and activator of transcription 6 (STAT6) was confirmed as a direct target of miR‑361‑5p by a dual‑luciferase reporter assay. Moreover, inhibition of STAT6 by small interfering RNA or miR‑361‑5p also decreased the expression of B-cell lymphoma extra large (Bcl-xL). In vivo, miR‑361‑5p significantly reduced tumor growth in a nude mouse xenograft model, and suppressed STAT6 and Bcl-xL expression. In conclusion, the present study indicated that miR‑361‑5p may represent a novel molecular tool for therapeutic and diagnostic strategies in NSCLC.

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1	Xue C, Hu Z, Jiang W, Zhao Y, Xu F, Huang Y, Zhao H, Wu J, Zhang Y, Zhao L, et al: National survey of the medical treatment status for non-small cell lung cancer (NSCLC) in China. Lung Cancer. 77:371–375. 2012. View Article : Google Scholar : PubMed/NCBI
2	Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI
3	Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T and Mitsudomi T: Mutations of the epidermal growth factor receptor gene in lung cancer: Biological and clinical implications. Cancer Res. 64:8919–8923. 2004. View Article : Google Scholar : PubMed/NCBI
4	Mitsudomi T, Viallet J, Mulshine JL, Linnoila RI, Minna JD and Gazdar AF: Mutations of ras genes distinguish a subset of non-small-cell lung cancer cell lines from small-cell lung cancer cell lines. Oncogene. 6:1353–1362. 1991.PubMed/NCBI
5	Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J, Stevens C, O'Meara S, Smith R, Parker A, et al: Lung cancer: Intragenic ERBB2 kinase mutations in tumours. Nature. 431:525–526. 2004. View Article : Google Scholar : PubMed/NCBI
6	Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, et al: Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 363:733–742. 2010. View Article : Google Scholar : PubMed/NCBI
7	Schilsky RL: Personalized medicine in oncology: The future is now. Nat Rev Drug Discov. 9:363–366. 2010. View Article : Google Scholar : PubMed/NCBI
8	Gerber DE and Minna JD: ALK inhibition for non-small cell lung cancer: From discovery to therapy in record time. Cancer Cell. 18:548–551. 2010. View Article : Google Scholar : PubMed/NCBI
9	McManus MT and Sharp PA: Gene silencing in mammals by small interfering RNAs. Nat Rev Genet. 3:737–747. 2002. View Article : Google Scholar : PubMed/NCBI
10	Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, Cheng CL, Yu CJ, Lee YC, Chen HS, et al: MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 13:48–57. 2008. View Article : Google Scholar : PubMed/NCBI
11	Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
12	Wang ZX, Bian HB, Wang JR, Cheng ZX, Wang KM and De W: Prognostic significance of serum miRNA-21 expression in human non-small cell lung cancer. J Surg Oncol. 104:847–851. 2011. View Article : Google Scholar : PubMed/NCBI
13	Larzabal L, de Aberasturi AL, Redrado M, Rueda P, Rodriguez MJ, Bodegas ME, Montuenga LM and Calvo A: TMPRSS4 regulates levels of integrin α5 in NSCLC through miR-205 activity to promote metastasis. Br J Cancer. 110:764–774. 2014. View Article : Google Scholar : PubMed/NCBI
14	Foss KM, Sima C, Ugolini D, Neri M, Allen KE and Weiss GJ: MiR-1254 and miR-574-5p: Serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 6:482–488. 2011. View Article : Google Scholar : PubMed/NCBI
15	Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, Muller RU, Straka E, Su L, Burki EA, et al: A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Res. 68:8535–8540. 2008. View Article : Google Scholar : PubMed/NCBI
16	Roth C, Stückrath I, Pantel K, Izbicki JR, Tachezy M and Schwarzenbach H: Low levels of cell-free circulating miR-361-3p and miR-625^* as blood-based markers for discriminating malignant from benign lung tumors. PLoS One. 7:e382482012. View Article : Google Scholar
17	Watahiki A and Wang Y, Morris J, Dennis K, O'Dwyer HM, Gleave M, Gout PW and Wang Y: MicroRNAs associated with metastatic prostate cancer. PLoS One. 6:e249502011. View Article : Google Scholar : PubMed/NCBI
18	Khella HW, White NM, Faragalla H, Gabril M, Boazak M, Dorian D, Khalil B, Antonios H, Bao TT, Pasic MD, et al: Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses. Tumor Biol. 33:131–140. 2012. View Article : Google Scholar
19	Kanitz A, Imig J, Dziunycz PJ, Primorac A, Galgano A, Hofbauer GF, Gerber AP and Detmar M: The expression levels of microRNA-361-5p and its target VEGFA are inversely correlated in human cutaneous squamous cell carcinoma. PLoS One. 7:e495682012. View Article : Google Scholar : PubMed/NCBI
20	Liu D, Tao T, Xu B, Chen S, Liu C, Zhang L, Lu K, Huang Y, Jiang L, Zhang X, et al: MiR-361-5p acts as a tumor suppressor in prostate cancer by targeting signal transducer and activator of transcription-6 (STAT6). Biochem Biophys Res Commun. 445:151–156. 2014. View Article : Google Scholar : PubMed/NCBI
21	Humphrey PA: Gleason grading and prognostic factors in carcinoma of the prostate. Mod Pathol. 17:292–306. 2004. View Article : Google Scholar : PubMed/NCBI
22	Kertesz M, Iovino N, Unnerstall U, Gaul U and Segal E: The role of site accessibility in microRNA target recognition. Nature Genetics. 39:1278–1284. 2007. View Article : Google Scholar : PubMed/NCBI
23	Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD and Kloecker GH: Exosomal microRNA: A diagnostic marker for lung cancer. Clin Lung Cancer. 10:42–46. 2009. View Article : Google Scholar : PubMed/NCBI
24	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
25	Zhang JG, Wang JJ, Zhao F, Liu Q, Jiang K and Yang GH: MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta. 411:846–852. 2010. View Article : Google Scholar : PubMed/NCBI
26	Romano G, Acunzo M, Garofalo M, Di Leva G, Cascione L, Zanca C, Bolon B, Condorelli G and Croce CM: MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Proc Natl Acad Sci USA. 109:16570–16575. 2012. View Article : Google Scholar : PubMed/NCBI
27	Guan P, Yin Z, Li X, Wu W and Zhou B: Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res. 31:542012. View Article : Google Scholar : PubMed/NCBI
28	Wang Q, Wang S, Wang H, Li P and Ma Z: MicroRNAs: Novel biomarkers for lung cancer diagnosis, prediction and treatment. Exp Biol Med (Maywood). 237:227–235. 2012. View Article : Google Scholar
29	Wu X, Xi X, Yan Q, Zhang Z, Cai B, Lu W and Wan X: MicroRNA-361-5p facilitates cervical cancer progression through mediation of epithelial-to-mesenchymal transition. Med Oncol. 30:7512013. View Article : Google Scholar : PubMed/NCBI
30	Wurster AL, Tanaka T and Grusby MJ: The biology of Stat4 and Stat6. Oncogene. 19:2577–2584. 2000. View Article : Google Scholar : PubMed/NCBI
31	Das S, Shetty P, Valapala M, Dasgupta S, Gryczynski Z and Vishwanatha JK: Signal transducer and activator of transcription 6 (STAT6) is a novel interactor of annexin A2 in prostate cancer cells. Biochemistry. 49:2216–2226. 2010. View Article : Google Scholar : PubMed/NCBI
32	Li BH, Yang XZ, Li PD, Yuan Q, Liu XH, Yuan J and Zhang WJ: IL-4/Stat6 activities correlate with apoptosis and metastasis in colon cancer cells. Biochem Biophys Res Commun. 369:554–560. 2008. View Article : Google Scholar : PubMed/NCBI
33	Cui X, Zhang L, Luo J, Rajasekaran A, Hazra S, Cacalano N and Dubinett SM: Unphosphorylated STAT6 contributes to constitutive cyclooxygenase-2 expression in human non-small cell lung cancer. Oncogene. 26:4253–4260. 2007. View Article : Google Scholar : PubMed/NCBI
34	Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, Ogawa M, Mitsudomi T, Sugiura T and Takahashi T: Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 58:3761–3764. 1998.PubMed/NCBI
35	Ostrand-Rosenberg S, Grusby MJ and Clements VK: Cutting edge: STAT6-deficient mice have enhanced tumor immunity to primary and metastatic mammary carcinoma. J Immunol. 165:6015–6019. 2000. View Article : Google Scholar : PubMed/NCBI