miR‑221‑3p promotes the cell growth of non‑small cell lung cancer by targeting p27

Yin,Guoqing; Zhang,Bo; Li,Jia

doi:10.3892/mmr.2019.10291

miR‑221‑3p promotes the cell growth of non‑small cell lung cancer by targeting p27

Authors:
- Guoqing Yin
- Bo Zhang
- Jia Li
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Affiliations: Department of Oncology, Xianyang Hospital, Yan'an University, Xianyang, Shaanxi 712000, P.R. China, Radiation Department, People's Hospital of Ankang City, Ankang, Shaanxi 725000, P.R. China, Department of Respiratory Medicine, Longnan Hospital, Daqing, Heilongjiang 163453, P.R. China
Published online on: May 23, 2019 https://doi.org/10.3892/mmr.2019.10291
Pages: 604-612
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Emerging evidence suggests the critical function of microRNAs in regulating the growth of cancer cells. In the present study, it was demonstrated that miR‑221‑3p was overexpressed in non‑small cell lung cancer (NSCLC) tissues and cell lines compared with that noted in the normal controls. Downregulation of miR‑221‑3p suppressed the proliferation, colony formation and invasion of NSCLC cells. To further understand the molecular mechanisms underlying the potential oncogenic function of miR‑221‑3p in NSCLC, the downstream targets of miR‑221‑3p were predicted using bioinformatic databases. The prediction suggested the cell cycle regulator p27 as one of the targets of miR‑221‑3p. Molecular experiments showed that miR‑221‑3p was able to bind with the 3'‑untranslated region (UTR) of p27 and decreased the expression of p27 in NSCLC cells. Consistent with the suppressive role of p27 in controlling cell cycle progression, overexpression of miR‑221‑3p decreased the expression of p27 and promoted cell cycle progression from G1 to S phase. Collectively, our findings identified miR‑221‑3p as a novel regulator of NSCLC cell growth via modulating the expression of p27.

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1	Vestergaard HH, Christensen MR and Lassen UN: A systematic review of targeted agents for non-small cell lung cancer. Acta Oncol. 57:176–186. 2018. View Article : Google Scholar : PubMed/NCBI
2	Xiong Y, Wang T, Wang M, Zhao J, Li X, Zhang Z, Zhou Y, Liu J, Jia L and Han Y: Long non-coding RNAs function as novel predictors and targets of non-small cell lung cancer: A systematic review and meta-analysis. Oncotarget. 9:11377–11386. 2018. View Article : Google Scholar : PubMed/NCBI
3	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
5	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI
6	Mohr AM and Mott JL: Overview of microRNA biology. Semin Liver Dis. 35:3–11. 2015. View Article : Google Scholar : PubMed/NCBI
7	Kwak PB, Iwasaki S and Tomari Y: The microRNA pathway and cancer. Cancer Sci. 101:2309–2315. 2010. View Article : Google Scholar : PubMed/NCBI
8	Farazi TA, Spitzer JI, Morozov P and Tuschl T: miRNAs in human cancer. J Pathol. 223:102–115. 2011. View Article : Google Scholar : PubMed/NCBI
9	Gentilin E, Degli Uberti E and Zatelli MC: Strategies to use microRNAs as therapeutic targets. Best Pract Res Clin Endocrinol Metab. 30:629–639. 2016. View Article : Google Scholar : PubMed/NCBI
10	Ma R, Wang C, Wang J, Wang D and Xu J: miRNA-mRNA interaction network in non-small-cell lung cancer. Interdiscip Sci. 8:209–219. 2016. View Article : Google Scholar : PubMed/NCBI
11	Zhang W, Zhang Q, Zhang M, Zhang Y, Li F and Lei P: Analysis for the mechanism between the small cell lung cancer and non-small cell lung cancer combing the miRNA and mRNA expression profiles. Thorac Cancer. 6:70–79. 2015. View Article : Google Scholar : PubMed/NCBI
12	Yu T, Liu L, Li J, Yan M, Lin H, Liu Y, Chu D, Tu H, Gu A and Yao M: MiRNA-10a is upregulated in NSCLC and may promote cancer by targeting PTEN. Oncotarget. 6:30239–30250. 2015. View Article : Google Scholar : PubMed/NCBI
13	Jiang Z, Yin J, Fu W, Mo Y, Pan Y, Dai L, Huang H, Li S and Zhao J: MiRNA 17 family regulates cisplatin-resistant and metastasis by targeting TGFbetaR2 in NSCLC. PLoS One. 9:e946392014. View Article : Google Scholar : PubMed/NCBI
14	Sun C, Li S, Yang C, Xi Y, Wang L, Zhang F and Li D: MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6. Biochem Biophys Res Commun. 471:82–88. 2016. View Article : Google Scholar : PubMed/NCBI
15	Wei WF, Zhou CF, Wu XG, He LN, Wu LF, Chen XJ, Yan RM, Zhong M, Yu YH, Liang L and Wang W: MicroRNA-221-3p, a TWIST2 target, promotes cervical cancer metastasis by directly targeting THBS2. Cell Death Dis. 8:32202017. View Article : Google Scholar : PubMed/NCBI
16	Li F, Xu JW, Wang L, Liu H, Yan Y and Hu SY: MicroRNA-221-3p is up-regulated and serves as a potential biomarker in pancreatic cancer. Artif Cells Nanomed Biotechnol. 46:482–487. 2018. View Article : Google Scholar : PubMed/NCBI
17	Shi J, Zhang Y, Jin N, Li Y, Wu S and Xu L: MicroRNA-221-3p plays an oncogenic role in gastric carcinoma by inhibiting PTEN expression. Oncol Res. 25:523–536. 2017. View Article : Google Scholar : PubMed/NCBI
18	Deng L, Lei Q, Wang Y, Wang Z, Xie G, Zhong X, Wang Y, Chen N, Qiu Y, Pu T, et al: Downregulation of miR-221-3p and upregulation of its target gene PARP1 are prognostic biomarkers for triple negative breast cancer patients and associated with poor prognosis. Oncotarget. 8:108712–108725. 2017. View Article : Google Scholar : PubMed/NCBI
19	Garofalo M, Quintavalle C, Romano G, Croce CM and Condorelli G: miR221/222 in cancer: Their role in tumor progression and response to therapy. Curr Mol Med. 12:27–33. 2012. View Article : Google Scholar : PubMed/NCBI
20	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
21	Yi Y, Zhao Y, Li C, Zhang L, Huang H, Li Y, Liu L, Hou P, Cui T, Tan P, et al: RAID v2.0: An updated resource of RNA-associated interactions across organisms. Nucleic Acids Res. 45:D115–D118. 2017. View Article : Google Scholar : PubMed/NCBI
22	Raghu D, Paul PJ, Gulati T, Deb S, Khoo C, Russo A, Gallo E, Blandino G, Chan AL, Takano E, et al: E6AP promotes prostate cancer by reducing p27 expression. Oncotarget. 8:42939–42948. 2017. View Article : Google Scholar : PubMed/NCBI
23	Vasile Bochis O, Achimas-Cadariu P, Vlad C, Fetica B, Corneliu Leucuta D, Ioan Busuioc C and Irimie A: The prognostic role of Skp2 and the tumor suppressor protein p27 in colorectal cancer. J BUON. 22:1122–1130. 2017.PubMed/NCBI
24	Ventura C, Nunez M, Gaido V, Pontillo C, Miret N, Randi A and Cocca C: Hexachlorobenzene alters cell cycle by regulating p27-cyclin E-CDK2 and c-Src-p27 protein complexes. Toxicol Lett. 270:72–79. 2017. View Article : Google Scholar : PubMed/NCBI
25	Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, Liu CG, Croce CM and Condorelli G: MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene. 27:3845–3855. 2008. View Article : Google Scholar : PubMed/NCBI
26	Zhou CF, Ma J, Huang L, Yi HY, Zhang YM, Wu XG, Yan RM, Liang L, Zhong M, Yu YH, et al: Cervical squamous cell carcinoma-secreted exosomal miR-221-3p promotes lymphangiogenesis and lymphatic metastasis by targeting VASH1. Oncogene. 38:1256–1268. 2019. View Article : Google Scholar : PubMed/NCBI
27	Wu Q, Ren X, Zhang Y, Fu X, Li Y, Peng Y, Xiao Q, Li T, Ouyang C, Hu Y, et al: MiR-221-3p targets ARF4 and inhibits the proliferation and migration of epithelial ovarian cancer cells. Biochem Biophys Res Commun. 497:1162–1170. 2018. View Article : Google Scholar : PubMed/NCBI
28	Wu D, Huang Y, Kang J, Li K, Bi X, Zhang T, Jin N, Hu Y, Tan P, Zhang L, et al: ncRDeathDB: A comprehensive bioinformatics resource for deciphering network organization of the ncRNA-mediated cell death system. Autophagy. 11:1917–1926. 2015. View Article : Google Scholar : PubMed/NCBI
29	Sgambato A, Cittadini A, Faraglia B and Weinstein IB: Multiple functions of p27(Kip1) and its alterations in tumor cells: A review. J Cell Physiol. 183:18–27. 2000. View Article : Google Scholar : PubMed/NCBI
30	Guan X, Wang Y, Xie R, Chen L, Bai J, Lu J and Kuo MT: p27(Kip1) as a prognostic factor in breast cancer: A systematic review and meta-analysis. J Cell Mol Med. 14:944–953. 2010. View Article : Google Scholar : PubMed/NCBI
31	Borriello A, Bencivenga D, Criscuolo M, Caldarelli I, Cucciolla V, Tramontano A, Borgia A, Spina A, Oliva A, Naviglio S and Della Ragione F: Targeting p27Kip1 protein: Its relevance in the therapy of human cancer. Expert Opin Ther Targets. 15:677–693. 2011. View Article : Google Scholar : PubMed/NCBI
32	Wander SA, Zhao D and Slingerland JM: p27: A barometer of signaling deregulation and potential predictor of response to targeted therapies. Clin Cancer Res. 17:12–18. 2011. View Article : Google Scholar : PubMed/NCBI
33	Sharma SS and Pledger WJ: The non-canonical functions of p27(Kip1) in normal and tumor biology. Cell Cycle. 15:1189–1201. 2016. View Article : Google Scholar : PubMed/NCBI
34	Fernandez S, Risolino M and Verde P: A novel miRNA-mediated STOP sign in lung cancer: miR-340 inhibits the proliferation of lung cancer cells through p27(KIP1). Mol Cell Oncol. 2:e9771472015. View Article : Google Scholar : PubMed/NCBI
35	Wang C, Ba X, Guo Y, Sun D, Jiang H, Li W, Huang Z, Zhou G, Wu S, Zhang J and Chen J: MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma. Sci Rep. 7:414562017. View Article : Google Scholar : PubMed/NCBI
36	Wang Y, Zeng J, Pan J, Geng X, Liu Y, Wu J, Song P, Wang Y, Jia J and Wang L: MicroRNA-200c is involved in proliferation of gastric cancer by directly repressing p27(Kip1). Biochem Biophys Rep. 8:227–233. 2016.PubMed/NCBI
37	Yang YF, Wang F, Xiao JJ, Song Y, Zhao YY, Cao Y, Bei YH and Yang CQ: MiR-222 overexpression promotes proliferation of human hepatocellular carcinoma HepG2 cells by downregulating p27. Int J Clin Exp Med. 7:893–902. 2014.PubMed/NCBI
38	Sarkar S, Dubaybo H, Ali S, Goncalves P, Kollepara SL, Sethi S, Philip PA and Li Y: Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA. Am J Cancer Res. 3:465–477. 2013.PubMed/NCBI
39	Zhang T, Tan P, Wang L, Jin N, Li Y, Zhang L, Yang H, Hu Z, Zhang L, Hu C, et al: RNALocate: A resource for RNA subcellular localizations. Nucleic Acids Res. 45:D135–D138. 2017.PubMed/NCBI
40	Cui T, Zhang L, Huang Y, Yi Y, Tan P, Zhao Y, Hu Y, Xu L, Li E and Wang D: MNDR v2.0: An updated resource of ncRNA-disease associations in mammals. Nucleic Acids Res. 46:D371–D374. 2018.PubMed/NCBI
41	Li Y, Wang C, Miao Z, Bi X, Wu D, Jin N, Wang L, Wu H, Qian K, Li C, et al: ViRBase: A resource for virus-host ncRNA-associated interactions. Nucleic Acids Res. 43:D578–D582. 2015. View Article : Google Scholar : PubMed/NCBI