miR‑140‑5p regulates cell migration and invasion of non‑small cell lung cancer cells through targeting VEGFA

Yang,Peixia; Xiong,Jie; Zuo,Lin; Liu,Kequn; Zhang,Houbin

doi:10.3892/mmr.2018.9291

miR‑140‑5p regulates cell migration and invasion of non‑small cell lung cancer cells through targeting VEGFA

Authors:
- Peixia Yang
- Jie Xiong
- Lin Zuo
- Kequn Liu
- Houbin Zhang
View Affiliations

Affiliations: Respiratory Department of Internal Medicine, Linyi Central Hospital, Linyi, Shandong 276000, P.R. China, Department of Internal Medicine, Health Service Center of Lanshan District, Linyi, Shandong 276000, P.R. China, Department of Hemodialysis, People's Hospital of Yishui County, Linyi, Shandong 276000, P.R. China, Department of Thoracic Surgery, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China
Published online on: July 16, 2018 https://doi.org/10.3892/mmr.2018.9291
Pages: 2866-2872
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Lung cancer is the most common type of cancer worldwide, the most prevalent form of which is non‑small cell lung cancer (NSCLC). MicroRNAs (miRs) are involved in the progression of NSCLC; however, the specific function of miR‑140‑5p in NSCLC remains unclear. The present study demonstrated that miR‑140‑5p was downregulated in the tumor tissues of patients with NSCLC, and it was associated with a poor prognosis. Furthermore, miR‑140‑5p significantly suppressed cell migration and invasion of the NSCLC cell line A549. In addition, the direct regulatory effect of miR‑140‑5p on vascular endothelial growth factor‑A (VEGFA) was predicted by TargetScan and verified using a luciferase reporter gene assay. The present study also hypothesized that miR‑140‑5p may inhibit the expression of phosphorylated‑protein kinase B by targeting VEGFA. In conclusion, miR‑140‑5p may be a potential target for the development of anti‑neoplastic therapies in lung cancer.

View Figures

View References

1	Molina JR, Yang P, Cassivi SD, Schild SE and Adjei AA: Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 83:584–594. 2008. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
3	Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L and Kunkler I: EUROCARE-4 Working Group: Recent cancer survival in Europe: A 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol. 8:784–796. 2007. 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	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
6	Ruan K, Fang X and Ouyang G: MicroRNAs: Novel regulators in the hallmarks of human cancer. Cancer Lett. 285:116–126. 2009. View Article : Google Scholar : PubMed/NCBI
7	Lan H, Chen W, He G and Yang S: miR-140-5p inhibits ovarian cancer growth partially by repression of PDGFRA. Biomed Pharmacother. 75:117–122. 2015. View Article : Google Scholar : PubMed/NCBI
8	Lu Y, Qin T, Li J, Wang L, Zhang Q, Jiang Z and Mao J: MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer. Cancer Gene Ther. 24:386–392. 2017. View Article : Google Scholar : PubMed/NCBI
9	Petrovic N: Targeting angiogenesis in cancer treatments: Where do we stand? J Pharm Pharm Sci. 19:226–238. 2016. View Article : Google Scholar : PubMed/NCBI
10	Shinkaruk S, Bayle M, Laïn G and Déléris G: Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy. Curr Med Chem Anticancer Agents. 3:95–117. 2003. View Article : Google Scholar : PubMed/NCBI
11	Yang J, Yang D, Sun Y, Sun B, Wang G, Trent JC, Araujo DM, Chen K and Zhang W: Genetic amplification of the vascular endothelial growth factor (VEGF) pathway genes, including VEGFA, in human osteosarcoma. Cancer. 117:4925–4938. 2011. View Article : Google Scholar : PubMed/NCBI
12	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
13	Yuan Y, Shen Y, Xue L and Fan H: miR-140 suppresses tumor growth and metastasis of non-small cell lung cancer by targeting insulin-like growth factor 1 receptor. PLoS One. 8:e736042013. View Article : Google Scholar : PubMed/NCBI
14	Zhai H, Fesler A, Ba Y, Wu S and Ju J: Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy. Oncotarget. 6:19735–19746. 2015. View Article : Google Scholar : PubMed/NCBI
15	Fang Z, Yin S, Sun R, Zhang S, Fu M, Wu Y, Zhang T, Khaliq J and Li Y: miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1. Mol Cancer. 16:1392017. View Article : Google Scholar : PubMed/NCBI
16	Jeannot V, Busser B, Brambilla E, Wislez M, Robin B, Cadranel J, Coll JL and Hurbin A: The PI3K/AKT pathway promotes gefitinib resistance in mutant KRAS lung adenocarcinoma by a deacetylase-dependent mechanism. Int J Cancer. 134:2560–2571. 2014. View Article : Google Scholar : PubMed/NCBI
17	Chen HY, Yu SL, Chen CH, Chang GC, Chen CY, Yuan A, Cheng CL, Wang CH, Terng HJ, Kao SF, et al: A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med. 356:11–20. 2007. View Article : Google Scholar : PubMed/NCBI
18	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
19	Zhao D, Pan C, Sun J, Gilbert C, Drews-Elger K, Azzam DJ, Picon-Ruiz M, Kim M, Ullmer W, El-Ashry D, et al: VEGF drives cancer-initiating stem cells through VEGFR-2/Stat3 signaling to upregulate Myc and Sox2. Oncogene. 34:3107–3119. 2014. View Article : Google Scholar : PubMed/NCBI
20	Gu A, Lu J, Wang W, Shi C, Han B and Yao M: Role of miR-497 in VEGF-A-mediated cancer cell growth and invasion in non-small cell lung cancer. Int J Biochem Cell Biol. 70:118–125. 2016. View Article : Google Scholar : PubMed/NCBI
21	Ghosh A, Dasgupta D, Ghosh A, Roychoudhury S, Kumar D, Gorain M, Butti R, Datta S, Agarwal S, Gupta S, et al: MiRNA199a-3p suppresses tumor growth, migration, invasion and angiogenesis in hepatocellular carcinoma by targeting VEGFA, VEGFR1, VEGFR2, HGF and MMP2. Cell Death Dis. 8:e27062017. View Article : Google Scholar : PubMed/NCBI
22	Geng J, Li X, Zhou Z, Wu CL, Dai M and Bai X: EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer. Cancer Lett. 359:275–287. 2015. View Article : Google Scholar : PubMed/NCBI
23	Osaki M, Oshimura M and Ito H: PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis. 9:667–676. 2004. View Article : Google Scholar : PubMed/NCBI
24	Shiojima I and Walsh K: Role of Akt signaling in vascular homeostasis and angiogenesis. Circ Res. 90:1243–1250. 2002. View Article : Google Scholar : PubMed/NCBI
25	Hudson C, Liu M, Chiang G, Otterness D, Loomis D, Kaper F, Giaccia A and Abraham R: Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol. 22:7004–7014. 2002. View Article : Google Scholar : PubMed/NCBI
26	Liu GT, Chen HT, Tsou HK, Tan TW, Fong YC, Chen PC, Yang WH, Wang SW, Chen JC and Tang CH: CCL5 promotes VEGF-dependent angiogenesis by down-regulating miR-200b through PI3K/Akt signaling pathway in human chondrosarcoma cells. Oncotarget. 5:10718–10731. 2014. View Article : Google Scholar : PubMed/NCBI
27	Qi L, Zhu F, Li SH, Si LB, Hu LK and Tian H: Retinoblastoma binding protein 2 (RBP2) promotes HIF-1α-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway. PLoS One. 9:e1060322014. View Article : Google Scholar : PubMed/NCBI