lncRNA PVT1 promotes the angiogenesis of vascular endothelial cell by targeting miR‑26b to activate CTGF/ANGPT2

Zheng,Jifu; Hu,Lili; Cheng,Jing; Xu,Jing; Zhong,Zhiqiang; Yang,Yuan; Yuan,Zheng

doi:10.3892/ijmm.2018.3595

lncRNA PVT1 promotes the angiogenesis of vascular endothelial cell by targeting miR‑26b to activate CTGF/ANGPT2

Authors:
- Jifu Zheng
- Lili Hu
- Jing Cheng
- Jing Xu
- Zhiqiang Zhong
- Yuan Yang
- Zheng Yuan
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Affiliations: Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: March 29, 2018 https://doi.org/10.3892/ijmm.2018.3595
Pages: 489-496

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Abstract

Angiogenesis is essential for various biological processes, including tumor blood supply delivery, cancer cell growth, invasion and metastasis. Plasmacytoma variant translocation 1 (PVT1) long noncoding RNA (lncRNA) has been previously reported to affect angiogenesis of glioma microvascular endothelial cells by regulating microRNA (miR)‑186 expression level. However, the specific underlying molecular mechanism of PVT1 regulation of angiogenesis in vascular endothelial cells remains to be elucidated. The present study investigated the role of PVT1 in cell proliferation, migration and vascular tube formation of human umbilical vein endothelial cells (HUVECs) using MTT assay, Transwell migration assay and in vitro vascular tube formation assay, respectively. In order to determine the effect of miR‑26b on cell proliferation, migration and vascular tube formation of HUVECs, miR‑26 mimic or miR‑26b inhibitor were transfected into HUVECs. Reverse transcription‑quantitative polymerase chain reaction and western blotting were conducted to quantify the mRNA and protein expression levels of target genes. The present study confirmed that miR‑26b bound 3'‑untranslated region (3'‑UTR) and subsequently influenced gene expression level using dual luciferase reporter assay. The current study observed that PVT1 affected cell proliferation, migration and in vitro vascular tube formation of HUVECs. In addition, it was determined that PVT1 was able to bind and degrade miR‑26b to promote connective tissue growth factor (CTGF) and angiopoietin 2 (ANGPT2) expression. miR‑26b was also identified to have a suppressive role in cell proliferation, migration and in vitro vascular tube formation of HUVECs via binding 3'‑UTR regions and downregulating CTGF and ANGPT2 expression levels. The current findings may improve the understanding of the underlying mechanism of PVT1 contributing to angiogenesis of vascular endothelial cells and offer rationale for targeting PVT1 to treat angiogenesis dysfunction‑associated diseases, including cancer metastasis.

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1	Wang KC and Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell. 43:904–914. 2011. View Article : Google Scholar : PubMed/NCBI
2	Colombo T, Farina L, Macino G and Paci P: PVT1: A rising star among oncogenic long noncoding RNAs. BioMed Res Int. 2015:3042082015. View Article : Google Scholar : PubMed/NCBI
3	Yang YR, Zang SZ, Zhong CL, Li YX, Zhao SS and Feng XJ: Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. Int J Clin Exp Pathol. 7:6929–6935. 2014.PubMed/NCBI
4	Ding C, Yang Z, Lv Z, Du C, Xiao H, Peng C, Cheng S, Xie H, Zhou L, Wu J and Zheng S: Long non-coding RNA PVT1 is associated with tumor progression and predicts recurrence in hepatocellular carcinoma patients. Oncol Lett. 9:955–963. 2015. View Article : Google Scholar : PubMed/NCBI
5	Ding J, Li D, Gong M, Wang J, Huang X, Wu T and Wang C: Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer. Onco Targets Ther. 7:1625–1630. 2014. View Article : Google Scholar : PubMed/NCBI
6	Zheng X, Hu H and Li S: High expression of lncRNA PVT1 promotes invasion by inducing epithelial-to-mesenchymal transition in esophageal cancer. Oncol Lett. 12:2357–2362. 2016. View Article : Google Scholar : PubMed/NCBI
7	Shen CJ, Cheng YM and Wang CL: LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells. J Drug Target. 25:1–8. 2017. View Article : Google Scholar
8	Chunharojrith P, Nakayama Y, Jiang X, Kery RE, Ma J, De La Hoz Ulloa CS, Zhang X, Zhou Y and Klibanski A: Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line. Mol Cell Endocrinol. 416:27–35. 2015. View Article : Google Scholar :
9	Gordon FE, Nutt CL, Cheunsuchon P, Nakayama Y, Provencher KA, Rice KA, Zhou Y, Zhang X and Klibanski A: Increased expression of angiogenic genes in the brains of mouse meg3-null embryos. Endocrinology. 151:2443–2452. 2010. View Article : Google Scholar : PubMed/NCBI
10	Fu WM, Lu YF, Hu BG, Liang WC, Zhu X, Yang HD, Li G and Zhang JF: Long noncoding RNA Hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways. Oncotarget. 7:4712–4723. 2016. View Article : Google Scholar :
11	Ma Y, Wang P, Xue Y, Qu C, Zheng J, Liu X, Ma J and Liu Y: PVT1 affects growth of glioma microvascular endothelial cells by negatively regulating miR-186. Tumour Biol. 39:1010428317694326. 2017. View Article : Google Scholar
12	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
13	Yu J, Wang F, Yang GH, Wang FL, Ma YN, Du ZW and Zhang JW: Human microRNA clusters: Genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun. 349:59–68. 2006. View Article : Google Scholar : PubMed/NCBI
14	Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, et al: Identification of hundreds of conserved and nonconserved human microRNAs. Nature Genet. 37:766–770. 2005. View Article : Google Scholar : PubMed/NCBI
15	Brennecke J, Hipfner DR, Stark A, Russell RB and Cohen SM: Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 113:25–36. 2003. View Article : Google Scholar : PubMed/NCBI
16	Calame K: MicroRNA-155 function in B Cells. Immunity. 27:825–827. 2007. View Article : Google Scholar : PubMed/NCBI
17	Jopling CL, Yi M, Lancaster AM, Lemon SM and Sarnow P: Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 309:1577–1581. 2005. View Article : Google Scholar : PubMed/NCBI
18	Icli B, Dorbala P and Feinberg MW: An emerging role for the miR-26 family in cardiovascular disease. Trends Cardiovasc Med. 24:241–248. 2014. View Article : Google Scholar : PubMed/NCBI
19	Icli B, Wara AK, Moslehi J, Sun X, Plovie E, Cahill M, Marchini JF, Schissler A, Padera RF, Shi J, et al: MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling. Circ Res. 113:1231–1241. 2013. View Article : Google Scholar : PubMed/NCBI
20	Liu SC, Chuang SM, Hsu CJ, Tsai CH, Wang SW and Tang CH: CTGF increases vascular endothelial growth factor-dependent angiogenesis in human synovial fibroblasts by increasing miR-210 expression. Cell Death Dis. 5:e14852014. View Article : Google Scholar : PubMed/NCBI
21	Babic AM, Chen CC and Lau LF: Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo. Mol Cell Biol. 19:2958–2966. 1999. View Article : Google Scholar : PubMed/NCBI
22	Wang BJ, Ding HW and Ma GA: Long noncoding RNA PVT1 promotes melanoma progression via endogenous sponging miR-26b. Oncol Res. 2017. View Article : Google Scholar
23	Wang R, Ding X, Zhou S, Li M, Sun L, Xu X and Fei G: Microrna-26b attenuates monocrotaline-induced pulmonary vascular remodeling via targeting connective tissue growth factor (CTGF) and cyclin D1 (CCND1). Oncotarget. 7:72746–72757. 2016.
24	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
25	Kuo CH, Chen PK, Chang BI, Sung MC, Shi CS, Lee JS, Chang CF, Shi GY and Wu HL: The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen. Blood. 119:1302–1313. 2012. View Article : Google Scholar
26	Boettger T, Beetz N, Kostin S, Schneider J, Kruger M, Hein L and Braun T: Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest. 119:2634–2647. 2009. View Article : Google Scholar : PubMed/NCBI
27	Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, Richardson JA, Bassel-Duby R and Olson EN: MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev. 23:2166–2178. 2009. View Article : Google Scholar : PubMed/NCBI
28	Dorn GW 2nd, Matkovich SJ, Eschenbacher WH and Zhang Y: A human 3′ miR-499 mutation alters cardiac mRNA targeting and function. Circ Res. 110:958–967. 2012. View Article : Google Scholar : PubMed/NCBI
29	Duan G, Ren C, Zhang Y and Feng S: MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1. Tumour Biol. 36:6201–6209. 2015. View Article : Google Scholar
30	Guttman M, Amit I, Ga rber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI
31	Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, et al: Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA. 106:11667–11672. 2009. View Article : Google Scholar : PubMed/NCBI
32	Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, et al: A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 142:409–419. 2010. View Article : Google Scholar : PubMed/NCBI
33	Paci P, Colombo T and Farina L: Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer. BMC Syst Biol. 8:832014. View Article : Google Scholar : PubMed/NCBI