miR‑195 suppresses metastasis and angiogenesis of squamous cell lung cancer by inhibiting the expression of VEGF

Liu,Hailin; Chen,Yulong; Li,Yue; Li,Chenguang; Qin,Tingting; Bai,Ming; Zhang,Zhenfa; Jia,Rui; Su,Yanjun; Wang,Changli

doi:10.3892/mmr.2019.10496

miR‑195 suppresses metastasis and angiogenesis of squamous cell lung cancer by inhibiting the expression of VEGF

Authors:
- Hailin Liu
- Yulong Chen
- Yue Li
- Chenguang Li
- Tingting Qin
- Ming Bai
- Zhenfa Zhang
- Rui Jia
- Yanjun Su
- Changli Wang
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Affiliations: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
Published online on: July 12, 2019 https://doi.org/10.3892/mmr.2019.10496
Pages: 2625-2632
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs) are small, noncoding RNAs that are ~22 nucleotides in length. Accumulating evidence has revealed that miRNAs act as oncogenes or tumor suppressors in various human cancers. In order to investigate the role of miR‑195‑ in squamous cell lung cancer (SQCLC) cells, and to determine the underlying mechanism, the present study utilized RT‑qPCR, western blot analysis, luciferase assay, MTT assay, cell migration assay, and in vitro angiogenesis techniques. The results obtained revealed that miR‑195‑5p acted as a tumor suppressor in SQCLC cells. The expression levels of miR‑195 were decreased in two SQCLC cell lines (H520 and SK‑Mes‑1) compared with a normal lung cell line, and miR‑195 directly targeted the 3'‑untranslated region of vascular endothelial growth factor (VEGF) in SQCLC cells. Additionally, miR‑195 upregulation suppressed the viability and migration of SQCLC cells. Furthermore, miR‑195 inhibited the growth and tube formation of endothelial vascular cells. Collectively, the ﬁndings indicated that miR‑195 downregulated VEGF, and that targeting this miRNA may provide an effective approach to inhibit angiogenesis in tumors.

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1	Gandellini P, Doldi V and Zaffaroni N: microRNAs as players and signals in the metastatic cascade: Implications for the development of novel anti-metastatic therapies. Semin Cancer Biol. 44:132–140. 2017. View Article : Google Scholar : PubMed/NCBI
2	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
3	Zhou W, Wang S, Ying Y, Zhou R and Mao P: miR-196b/miR-1290 participate in the antitumor effect of resveratrol via regulation of IGFBP3 expression in acute lymphoblastic leukemia. Oncol Rep. 37:1075–1083. 2017. View Article : Google Scholar : PubMed/NCBI
4	Gartel AL and Kandel ES: miRNAs: Little known mediators of oncogenesis. Semin Cancer Biol. 18:103–110. 2008. View Article : Google Scholar : PubMed/NCBI
5	Kai K, Dittmar RL and Sen S: Secretory microRNAs as biomarkers of cancer. Semin Cell Dev Biol. 78:22–36. 2018. View Article : Google Scholar : PubMed/NCBI
6	Nambara S and Mimori K: MicroRNA in various aspects of cancer development. Gan To Kagaku Ryoho. 44:362–366. 2017.(In Japanese). PubMed/NCBI
7	Fang YX and Gao WQ: Roles of microRNAs during prostatic tumorigenesis and tumor progression. Oncogene. 33:135–147. 2014. View Article : Google Scholar : PubMed/NCBI
8	Su SF, Chang YW, Andreu-Vieyra C, Fang JY, Yang Z, Han B, Lee AS and Liang G: miR-30d, miR-181a and miR-199a-5p cooperatively suppress the endoplasmic reticulum chaperone and signaling regulator GRP78 in cancer. Oncogene. 32:4694–4701. 2013. View Article : Google Scholar : PubMed/NCBI
9	Yang J, Zhu J, Zhang YH, Chen YS, Ding LL, Kensler TW and Chen JG: Lung cancer in a rural area of China: Rapid rise in incidence and poor improvement in survival. Asian Pac J Cancer Prev. 16:7295–7302. 2015. View Article : Google Scholar : PubMed/NCBI
10	Yamano S, Gi M, Tago Y, Doi K, Okada S, Hirayama Y, Tachibana H, Ishii N, Fujioka M, Tatsumi K and Wanibuchi H: Role of deltaNp63posCD44vpos cells in the development of N-nitroso-tris-chloroethylurea-induced peripheral-type mouse lung squamous cell carcinomas. Cancer Sci. 107:123–132. 2016. View Article : Google Scholar : PubMed/NCBI
11	Zhang YC, Zhou Q and Wu YL: Emerging challenges of advanced squamous cell lung cancer. ESMO Open. 1:e0001292016. View Article : Google Scholar : PubMed/NCBI
12	Funai K, Yokose T, Ishii G, Araki K, Yoshida J, Nishimura M, Nagai K, Nishiwaki Y and Ochiai A: Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol. 27:978–984. 2003. View Article : Google Scholar : PubMed/NCBI
13	Griffiths-Jones S, Saini HK, Van Dongen S and Enright AJ: Enrigh: Tools for microRNA genomics. Nucleic Acids Res. 36:D154–D158. 2008. View Article : Google Scholar : PubMed/NCBI
14	Wang X, Wang Y, Lan H and Li J: MiR-195 inhibits the growth and metastasis of NSCLC cells by targeting IGF1R. Tumour Biol. 35:8765–8770. 2014. View Article : Google Scholar : PubMed/NCBI
15	Liu B, Qu J, Xu F, Guo Y, Wang Y, Yu H and Qian B: MiR-195 suppresses non-small cell lung cancer by targeting CHEK1. Oncotarget. 6:9445–9456. 2015.PubMed/NCBI
16	Han K, Chen X, Bian N, Ma B, Yang T, Cai C, Fan Q, Zhou Y and Zhao TB: MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1. Oncotarget. 6:8875–8889. 2015. View Article : Google Scholar : PubMed/NCBI
17	Wang R, Zhao N, Li S, Fang JH, Chen MX, Yang J, Jia WH, Yuan Y and Zhuang SM: MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42. Hepatology. 58:642–653. 2013. View Article : Google Scholar : PubMed/NCBI
18	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
19	Cai C, Chen QB, Han ZD, Zhang YQ, He HC, Chen JH, Chen YR, Yang SB, Wu YD, Zeng YR, et al: miR-195 inhibits tumor progression by targeting RPS6KB1 in human prostate cancer. Clin Cancer Res. 21:4922–4934. 2015. View Article : Google Scholar : PubMed/NCBI
20	Xu H, Hu YW, Zhao JY, Hu XM, Li SF, Wang YC, Gao JJ, Sha YH, Kang CM, Lin L, et al: MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma. Oncol Rep. 34:175–182. 2015. View Article : Google Scholar : PubMed/NCBI
21	Cai H, Zhao H, Tang J and Wu H: Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma. J Surg Res. 194:505–510. 2015. View Article : Google Scholar : PubMed/NCBI
22	Igglezou M, Vareli K, Georgiou GK, Sainis I and Briasoulis E: Kinetics of circulating levels of miR-195, miR-155 and miR-21 in patients with breast cancer undergoing mastectomy. Anticancer Res. 34:7443–7447. 2014.PubMed/NCBI
23	Lin L, Huang Y and Gong W: Inhibition of miR-92b suppresses nonsmall cell lung cancer cells growth and motility by targeting RECK. Mol Cell Biochem. 387:171–176. 2014. View Article : Google Scholar : PubMed/NCBI
24	Nishikawa R, Goto Y, Kojima S, Enokida H, Chiyomaru T, Kinoshita T, Sakamoto S, Fuse M, Nakagawa M, Naya Y, et al: Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer. Int J Oncol. 45:401–410. 2014. View Article : Google Scholar : PubMed/NCBI