MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2

Huang,Xiaori; Wang,Lei; Liu,Wei; Li,Fei

doi:10.3892/ol.2019.9954

MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2

Authors:
- Xiaori Huang
- Lei Wang
- Wei Liu
- Fei Li
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Affiliations: Department of Respiratory Medicine, People's Hospital of Rizhao, Rizhao, Shandong 276826, P.R. China
Published online on: January 21, 2019 https://doi.org/10.3892/ol.2019.9954
Pages: 3425-3431
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increasing number of microRNAs (miRNAs) have been reported to play an important role in the development and progression of non-small cell lung cancer (NSCLC). In particular, microRNA-497-5p (miR-497-5p) has been proposed as a tumor suppressor miRNA in human cancers. However, the role of miR-497-5p and its potential molecular mechanism associated with NSCLC are less studied. Therefore, the role of miR-497-5p in the pathogenesis of NSCLC was investigated. In the present study, the expression of miR-497-5p was significantly downregulated in NSCLC. Moreover, overexpression of miR-497-5p inhibited the proliferation and invasion of NSCLC cells by suppressing FGF2. In addition, FGF2 was a downstream target of miR-497-5p in NSCLC. FGF2 was upregulated in NSCLC promoting cell proliferation and invasion. Overexpression of FGF2 impaired the inhibitory effect of miR-497-5p in NSCLC. Taken together, these results demonstrate that miR-497-5p is a tumor suppressor miRNA and demonstrate its potential for future use in the treatment of human NSCLC.

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1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
2	Laskin JJ and Sandler AB: State of the art in therapy for non-small cell lung cancer. Cancer Invest. 23:427–442. 2005. View Article : Google Scholar : PubMed/NCBI
3	Ma L, Qiu B, Zhang J, Li QW, Wang B, Zhang XH, Qiang MY, Chen ZL, Guo SP and Liu H: Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy. Chin J Cancer. 36:932017. View Article : Google Scholar : PubMed/NCBI
4	Murray N: Reality check for pemetrexed and maintenance therapy in advanced non-small-cell lung cancer. J Clin Oncol. 32:482–483. 2014. View Article : Google Scholar : PubMed/NCBI
5	Ferguson MK: Diagnosing and staging of non-small cell lung cancer. Hematol Oncol Clin North Am. 4:1053–1068. 1990.PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Del Vescovo V, Grasso M, Barbareschi M and Denti MA: MicroRNAs as lung cancer biomarkers. World J Clin Oncol. 5:604–620. 2014. View Article : Google Scholar : PubMed/NCBI
8	Yao Y, Shen H, Zhou Y, Yang Z and Hu T: MicroRNA-215 suppresses the proliferation, migration and invasion of non-small cell lung carcinoma cells through the downregulation of matrix metalloproteinase-16 expression. Exp Ther Med. 15:3239–3246. 2018.PubMed/NCBI
9	Wei L and Ran F: MicroRNA-20a promotes proliferation and invasion by directly targeting early growth response 2 in non-small cell lung carcinoma. Oncol Lett. 15:271–277. 2018.PubMed/NCBI
10	Pang PC, Shi XY, Huang WL and Sun K: miR-497 as a potential serum biomarker for the diagnosis and prognosis of osteosarcoma. Eur Rev Med Pharmacol Sci. 20:3765–3769. 2016.PubMed/NCBI
11	Pengcheng S, Ziqi W, Luyao Y, Xiangwei Z, Liang L, Yuwei L, Lechen L and Wanhai X: MicroRNA-497 suppresses renal cell carcinoma by targeting VEGFR-2 in ACHN cells. Biosci Rep. 37:372017. View Article : Google Scholar
12	Wu R, Tang S, Wang M, Xu X, Yao C and Wang S: MicroRNA-497 induces apoptosis and suppresses proliferation via the Bcl-2/Bax-caspase9-caspase3 pathway and cyclin D2 protein in HUVECs. PLoS One. 11:e01670522016. View Article : Google Scholar : PubMed/NCBI
13	Tao L, Zhang CY, Guo L, Li X, Han NN, Zhou Q and Liu ZL: MicroRNA-497 accelerates apoptosis while inhibiting proliferation, migration, and invasion through negative regulation of the MAPK/ERK signaling pathway via RAF-1. J Cell Physiol. 233:6578–6588. 2017. View Article : Google Scholar
14	Hu J, Xu JF and Ge WL: MiR-497 enhances metastasis of oral squamous cell carcinoma through SMAD7 suppression. Am J Transl Res. 8:3023–3031. 2016.PubMed/NCBI
15	Song KH, Cho H, Kim S, Lee HJ, Oh SJ, Woo SR, Hong SO, Jang HS, Noh KH, Choi CH, et al: API5 confers cancer stem cell-like properties through the FGF2-NANOG axis. Oncogenesis. 6:e2852017. View Article : Google Scholar : PubMed/NCBI
16	Khurana A, Liu P, Mellone P, Lorenzon L, Vincenzi B, Datta K, Yang B, Linhardt RJ, Lingle W, Chien J, et al: HSulf-1 modulates FGF2- and hypoxia-mediated migration and invasion of breast cancer cells. Cancer Res. 71:2152–2161. 2011. View Article : Google Scholar : PubMed/NCBI
17	Coleman SJ, Chioni AM, Ghallab M, Anderson RK, Lemoine NR, Kocher HM and Grose RP: Nuclear translocation of FGFR1 and FGF2 in pancreatic stellate cells facilitates pancreatic cancer cell invasion. EMBO Mol Med. 6:467–481. 2014. View Article : Google Scholar : PubMed/NCBI
18	Joy A, Moffett J, Neary K, Mordechai E, Stachowiak EK, Coons S, Rankin-Shapiro J, Florkiewicz RZ and Stachowiak MK: Nuclear accumulation of FGF-2 is associated with proliferation of human astrocytes and glioma cells. Oncogene. 14:171–183. 1997. View Article : Google Scholar : PubMed/NCBI
19	Sooman L, Freyhult E, Jaiswal A, Navani S, Edqvist PH, Pontén F, Tchougounova E, Smits A, Elsir T, Gullbo J, et al: FGF2 as a potential prognostic biomarker for proneural glioma patients. Acta Oncol. 54:385–394. 2015. View Article : Google Scholar : PubMed/NCBI
20	Xue G, Yan HL, Zhang Y, Hao LQ, Zhu XT, Mei Q and Sun SH: c-Myc-mediated repression of miR-15-16 in hypoxia is induced by increased HIF-2α and promotes tumor angiogenesis and metastasis by upregulating FGF2. Oncogene. 34:1393–1406. 2015. View Article : Google Scholar : PubMed/NCBI
21	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
22	Yang CL, Zheng XL, Ye K, Ge H, Sun YN, Lu YF and Fan QX: MicroRNA-183 acts as a tumor suppressor in human non-small cell lung cancer by down-regulating MTA1. Cell Physiol Biochem. 46:93–106. 2018. View Article : Google Scholar : PubMed/NCBI
23	Liu M, Zhang Y, Zhang J, Cai H, Zhang C, Yang Z, Niu Y, Wang H, Wei X, Wang W, et al: MicroRNA-1253 suppresses cell proliferation and invasion of non-small-cell lung carcinoma by targeting WNT5A. Cell Death Dis. 9:1892018. View Article : Google Scholar : PubMed/NCBI
24	Wang J, Wang Y, Sun D, Bu J, Ren F, Liu B, Zhang S, Xu Z, Pang S and Xu S: miR-455-5p promotes cell growth and invasion by targeting SOCO3 in non-small cell lung cancer. Oncotarget. 8:114956–114965. 2017.PubMed/NCBI
25	Huang C, Ma R, Yue J, Li N, Li Z and Qi D: MiR-497 suppresses YAP1 and inhibits tumor growth in non-small cell lung cancer. Cell Physiol Biochem. 37:342–352. 2015. View Article : Google Scholar : PubMed/NCBI
26	Sun Z, Li A, Yu Z, Li X, Guo X and Chen R: MicroRNA-497-5p suppresses tumor cell growth of osteosarcoma by targeting ADP ribosylation factor-like protein 2. Cancer Biother Radiopharm. 32:371–378. 2017. View Article : Google Scholar : PubMed/NCBI
27	Wang P, Meng X, Huang Y, Lv Z, Liu J, Wang G, Meng W, Xue S, Zhang Q, Zhang P, et al: MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF. Oncotarget. 8:2825–2834. 2017.PubMed/NCBI
28	Xu Y, Chen J, Gao C, Zhu D, Xu X, Wu C and Jiang J: MicroRNA-497 inhibits tumor growth through targeting insulin receptor substrate 1 in colorectal cancer. Oncol Lett. 14:6379–6386. 2017.PubMed/NCBI
29	Li J, Zhang Y, Wang X and Zhao R: microRNA-497 overexpression decreases proliferation, migration and invasion of human retinoblastoma cells via targeting vascular endothelial growth factor A. Oncol Lett. 13:5021–5027. 2017. View Article : Google Scholar : PubMed/NCBI
30	Zhang L, Yu Z, Xian Y and Lin X: microRNA-497 inhibits cell proliferation and induces apoptosis by targeting YAP1 in human hepatocellular carcinoma. FEBS Open Bio. 6:155–164. 2016. View Article : Google Scholar : PubMed/NCBI
31	Ruan WD, Wang P, Feng S, Xue Y and Zhang B: MicroRNA-497 inhibits cell proliferation, migration, and invasion by targeting AMOT in human osteosarcoma cells. Onco 9Targets Ther. 9:303–313. 2016. View Article : Google Scholar
32	Cheng Z, Ma R, Tan W and Zhang L: MiR-152 suppresses the proliferation and invasion of NSCLC cells by inhibiting FGF2. Exp Mol Med. 46:e1122014. View Article : Google Scholar : PubMed/NCBI
33	Zhang X, Xu J, Jiang T, Liu G, Wang D and Lu Y: MicroRNA-195 suppresses colorectal cancer cells proliferation via targeting FGF2 and regulating Wnt/β-catenin pathway. Am J Cancer Res. 6:2631–2640. 2016.PubMed/NCBI
34	Hu Y, Qiu Y, Yagüe E, Ji W, Liu J and Zhang J: miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell Death Dis. 7:e22912016. View Article : Google Scholar : PubMed/NCBI
35	Sun XH, Geng XL, Zhang J and Zhang C: miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2). Tumour Biol. 36:2127–2134. 2015. View Article : Google Scholar : PubMed/NCBI
36	He Q, Ren X, Chen J, Li Y, Tang X, Wen X, Yang X, Zhang J, Wang Y, Ma J, et al: miR-16 targets fibroblast growth factor 2 to inhibit NPC cell proliferation and invasion via PI3K/AKT and MAPK signaling pathways. Oncotarget. 7:3047–3058. 2016.PubMed/NCBI