miR-202 functions as a tumor suppressor in non-small cell lung cancer by targeting STAT3 Retraction in /10.3892/mmr.2022.12811

Zhao,Zhonghai; Lv,Bin; Zhang,Li; Zhao,Nana; Lv,Yan

doi:10.3892/mmr.2017.6841

miR-202 functions as a tumor suppressor in non-small cell lung cancer by targeting STAT3

Retraction in: /10.3892/mmr.2022.12811

Authors:
- Zhonghai Zhao
- Bin Lv
- Li Zhang
- Nana Zhao
- Yan Lv
View Affiliations

Affiliations: Department of Thoracic Surgery, Yidu Central Hospital of Weifang, Qingzhou, Shandong 262500, P.R. China, Department of Thoracic Surgery, Anqiu People's Hospital, Anqiu, Shandong 262100, P.R. China
Published online on: June 22, 2017 https://doi.org/10.3892/mmr.2017.6841
Pages: 2281-2289

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs) are a group of non-protein‑coding, short single-stranded RNAs, which are considered as promising molecular markers and therapeutic targets in several cancers. The present study explored the expression patterns and functional roles of miR‑202 in non‑small cell lung cancer (NSCLC). The expression levels of miR‑202 were determined in NSCLC tissues and cell lines using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The functional impact of miR‑202 overexpression on NSCLC cell viability, migration and invasion were evaluated using Cell Counting Kit‑8 reagent and Transwell migration and invasion assays, respectively. The molecular mechanism underlying the tumor suppressive roles of miR‑202 on NSCLC was examined using bioinformatics analysis, luciferase reporter assay, RT‑qPCR and western blot analysis. In addition, signal transducer and activator of transcription (STAT) 3 was overexpressed to investigate the impact on miR‑202‑mediated tumor suppression in NSCLC. The results indicated that miR‑202 was downregulated in NSCLC tissues and cell lines, and was associated with tumor node metastasis stage and lymph node metastasis. Exogenous miR‑202 expression reduced NSCLC cell viability, migration and invasion. Furthermore, STAT3 was identified as a direct target gene of miR‑202 in NSCLC. STAT3 overexpression improved miR‑202‑impaired cell viability, migration and invasion. In conclusion, the present study revealed novel anticancer effects induced by miR‑202 upregulation in NSCLC, and indicated that STAT3 may be a molecular target of miR‑202.

View Figures

View References

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	Bilello KS, Murin S and Matthay RA: Epidemiology, etiology, and prevention of lung cancer. Clin Chest Med. 23:1–25. 2002. View Article : Google Scholar : PubMed/NCBI
3	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
4	Boffetta P and Nyberg F: Contribution of environmental factors to cancer risk. Br Med Bull. 68:71–94. 2003. View Article : Google Scholar : PubMed/NCBI
5	Didkowska J, Manczuk M, McNeill A, Powles J and Zatonski W: Lung cancer mortality at ages 35–54 in the European Union: Ecological study of evolving tobacco epidemics. BMJ. 331:189–191. 2005. View Article : Google Scholar : PubMed/NCBI
6	Ridge CA, McErlean AM and Ginsberg MS: Epidemiology of lung cancer. Semin Intervent Radiol. 30:93–98. 2013. View Article : Google Scholar : PubMed/NCBI
7	Paliogiannis P, Attene F, Cossu A, Budroni M, Cesaraccio R, Tanda F, Trignano M and Palmieri G: Lung cancer epidemiology in North Sardinia, Italy. Multidiscip Respir Med. 8:452013. View Article : Google Scholar : PubMed/NCBI
8	Zhang T, Zhang DM, Zhao D, Hou XM, Liu XJ, Ling XL and Ma SC: The prognostic value of osteopontin expression in non-small cell lung cancer: A meta-analysis. J Mol Histol. 45:533–540. 2014. View Article : Google Scholar : PubMed/NCBI
9	Dempke WC, Suto T and Reck M: Targeted therapies for non-small cell lung cancer. Lung Cancer. 67:257–274. 2010. View Article : Google Scholar : PubMed/NCBI
10	Janku F, Stewart DJ and Kurzrock R: Targeted therapy in non-small-cell lung cancer-is it becoming a reality? Nat Rev Clin Oncol. 7:401–414. 2010. View Article : Google Scholar : PubMed/NCBI
11	Reck M, Heigener DF, Mok T, Soria JC and Rabe KF: Management of non-small-cell lung cancer: Recent developments. Lancet. 382:709–719. 2013. View Article : Google Scholar : PubMed/NCBI
12	Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG and Shepherd FA: Non-small-cell lung cancer. Lancet. 378:1727–1740. 2011. View Article : Google Scholar : PubMed/NCBI
13	Rosell R, Bivona TG and Karachaliou N: Genetics and biomarkers in personalisation of lung cancer treatment. Lancet. 382:720–731. 2013. View Article : Google Scholar : PubMed/NCBI
14	Campayo M, Navarro A, Viñolas N, Diaz T, Tejero R, Gimferrer JM, Molins L, Cabanas ML, Ramirez J, Monzo M and Marrades R: Low miR-145 and high miR-367 are associated with unfavourable prognosis in resected nonsmall cell lung cancer. Eur Respir J. 41:1172–1178. 2013. View Article : Google Scholar : PubMed/NCBI
15	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
16	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
17	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005. View Article : Google Scholar : PubMed/NCBI
18	Filipowicz W, Bhattacharyya SN and Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 9:102–114. 2008. View Article : Google Scholar : PubMed/NCBI
19	Krol J, Loedige I and Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 11:597–610. 2010.PubMed/NCBI
20	Wu D, Niu X, Pan H, Zhou Y, Qu P and Zhou J: MicroRNA-335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1. Mol Med Rep. 13:4379–4385. 2016.PubMed/NCBI
21	Rahman MA, Salajegheh A, Smith RA and Lam AK: MicroRNA-126 suppresses proliferation of undifferentiated (BRAF (V600E) and BRAF (WT)) thyroid carcinoma through targeting PIK3R2 gene and repressing PI3K-AKT proliferation-survival signalling pathway. Exp Cell Res. 339:342–350. 2015. View Article : Google Scholar : PubMed/NCBI
22	Zheng K, Liu W, Liu Y, Jiang C and Qian Q: MicroRNA-133a suppresses colorectal cancer cell invasion by targeting Fascin1. Oncol Lett. 9:869–874. 2015.PubMed/NCBI
23	Li Y, Li Y, Liu J, Fan Y, Li X, Dong M, Liu H and Chen J: Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer. Cancer Biol Ther. 17:272–279. 2016. View Article : Google Scholar : PubMed/NCBI
24	Kitade Y and Akao Y: MicroRNAs and their therapeutic potential for human diseases: microRNAs, miR-143 and −145, function as anti-oncomirs and the application of chemically modified miR-143 as an anti-cancer drug. J Pharmacol Sci. 114:276–280. 2010. View Article : Google Scholar : PubMed/NCBI
25	Ventura A and Jacks T: MicroRNAs and cancer: Short RNAs go a long way. Cell. 136:586–591. 2009. View Article : Google Scholar : PubMed/NCBI
26	Yang T, Thakur A, Chen T, Yang L, Lei G, Liang Y, Zhang S, Ren H and Chen M: MicroRNA-15a induces cell apoptosis and inhibits metastasis by targeting BCL2L2 in non-small cell lung cancer. Tumour Biol. 36:4357–4365. 2015. View Article : Google Scholar : PubMed/NCBI
27	Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
28	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
29	Li W and He F: Monocyte to macrophage differentiation-associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancer. Biochem Biophys Res Commun. 450:844–850. 2014. View Article : Google Scholar : PubMed/NCBI
30	Landi MT, Zhao Y, Rotunno M, Koshiol J, Liu H, Bergen AW, Rubagotti M, Goldstein AM, Linnoila I, Marincola FM, et al: MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin Cancer Res. 16:430–441. 2010. View Article : Google Scholar : PubMed/NCBI
31	Izzotti A, Calin GA, Arrigo P, Steele VE, Croce CM and De Flora S: Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 23:806–812. 2009. View Article : Google Scholar : PubMed/NCBI
32	Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D and Bader AG: Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 70:5923–5930. 2010. View Article : Google Scholar : PubMed/NCBI
33	Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, Zeng Y, Miao R, Jin G, Ma H, et al: Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 118:2600–2608. 2008.PubMed/NCBI
34	Ma G, Zhang F, Dong X, Wang X and Ren Y: Low expression of microRNA-202 is associated with the metastasis of esophageal squamous cell carcinoma. Exp Ther Med. 11:951–956. 2016.PubMed/NCBI
35	Shen X, Guo Y, Yu J, Qi J, Shi W, Wu X, Ni H and Ju S: miRNA-202 in bone marrow stromal cells affects the growth and adhesion of multiple myeloma cells by regulating B cell-activating factor. Clin Exp Med. 16:307–316. 2016. View Article : Google Scholar : PubMed/NCBI
36	Zhang Y, Zheng D, Xiong Y, Xue C, Chen G, Yan B and Ye Q: miR-202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post-transcriptionally. FEBS Lett. 588:1913–1920. 2014. View Article : Google Scholar : PubMed/NCBI
37	Sun Z, Zhang T, Hong H, Liu Q and Zhang H: miR-202 suppresses proliferation and induces apoptosis of osteosarcoma cells by downregulating Gli2. Mol Cell Biochem. 397:277–283. 2014. View Article : Google Scholar : PubMed/NCBI
38	Lin Z, Song D, Wei H, Yang X, Liu T, Yan W and Xiao J: TGF-β1-induced miR-202 mediates drug resistance by inhibiting apoptosis in human osteosarcoma. J Cancer Res Clin Oncol. 142:239–246. 2016. View Article : Google Scholar : PubMed/NCBI
39	Meng X, Chen X, Lu P, Ma W, Yue D, Song L and Fan Q: MicroRNA-202 inhibits tumor progression by targeting LAMA1 in esophageal squamous cell carcinoma. Biochem Biophys Res Commun. 473:821–827. 2016. View Article : Google Scholar : PubMed/NCBI
40	Zhang D, Li Y, Tian J, Zhang H and Wang S: miR-202 promotes endometriosis by regulating SOX6 expression. Int J Clin Exp Med. 8:17757–17764. 2015.PubMed/NCBI
41	Wagner KU and Schmidt JW: The two faces of Janus kinases and their respective STATs in mammary gland development and cancer. J Carcinog. 10:322011. View Article : Google Scholar : PubMed/NCBI
42	Zhang Z, Ma J and Zhang L: STAT3 and ras-MAPK signal transduction pathway in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 8:23–27. 2005.(In Chinese). PubMed/NCBI
43	Hu FY, Wang LP, Hou LL, Yin G and Wang HC: The expressions of STAT3, WWOX and c-myc in human non small cell lung cancer tissue and correlativity analysis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 26:1203–1205. 1209.2010.(In Chinese).
44	Yin Z, Zhang Y, Li Y, Lv T, Liu J and Wang X: Prognostic significance of STAT3 expression and its correlation with chemoresistance of non-small cell lung cancer cells. Acta Histochem. 114:151–158. 2012. View Article : Google Scholar : PubMed/NCBI
45	Zhu BR, Cai JM, Tang GS, Li BL, Gao F, Cui JG and Liu HC: Effects of STAT3 antisense oligonucleotide on proliferation and apoptosis of non-small cell lung cancer cell line A549. Ai Zheng. 26:820–827. 2007.(In Chinese). PubMed/NCBI
46	Fofaria NM and Srivastava SK: STAT3 induces anoikis resistance, promotes cell invasion and metastatic potential in pancreatic cancer cells. Carcinogenesis. 36:142–150. 2015. View Article : Google Scholar : PubMed/NCBI
47	Dai L, Cheng L, Zhang X, Jiang Q, Zhang S, Wang S, Li Y, Chen X, DU T, Yang Y, et al: Plasmid-based STAT3-siRNA efficiently inhibits breast tumor growth and metastasis in mice. Neoplasma. 58:538–547. 2011. View Article : Google Scholar : PubMed/NCBI
48	Abdulghani J, Gu L, Dagvadorj A, Lutz J, Leiby B, Bonuccelli G, Lisanti MP, Zellweger T, Alanen K, Mirtti T, et al: Stat3 promotes metastatic progression of prostate cancer. Am J Pathol. 172:1717–1728. 2008. View Article : Google Scholar : PubMed/NCBI
49	Lin HY, Chiang CH and Hung WC: STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells. Br J Cancer. 109:731–738. 2013. View Article : Google Scholar : PubMed/NCBI