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

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.

Long noncoding RNA PVT1 contributes to vascular endothelial cell proliferation via inhibition of miR‑190a‑5p in diagnostic biomarker evaluation of chronic heart failure

“…Considering the critical regulatory role of PVT1 in the angiogenesis of ECs (17), the present study further focused on the effects of miR-190a-5p on the proliferation of ECs. miR-190a-5p expression in HUVECs was regulated by cell transfection.…”

“…Increased expression of lncRNA plasmacytoma variant translocation 1 (PVT1) was found in several heart-related abnormalities, such as cardiac hypertrophy (15) and atrial fibrosis (16). In addition, Zheng et al (17) showed the promotive effects of PVT1 on the angiogenesis of ECs. However, to the best of our knowledge, the role of PVT1 in CHF has rarely been investigated.…”

Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

“…miR-146a is known to be cardioprotective and to reduce infarct size in in vivo animal models of AMI [48]. miR-186 was shown to play a crucial role in vascular endothelial cell angiogenesis [49]. miR-221 was shown to inhibit autophagy after hypoxia and was postulated to be a possible target in treating ischemia-reperfusion injury [50].…”

Linear and circular PVT1 in hematological malignancies and immune response: two faces of the same coin

“…Indeed, PVT1-binding of miR-186 led to upregulation of the autophagy-promoting genes ATG7 and Beclin1, with increased migration of glioma vascular endothelial cells [123]. Similarly, PVT1 enhanced in vitro vascular tube formation of HUVECs by enforcing the expression of CTGF and ANGPT2, through miR-26b suppression [124]. The pro-angiogenic function of PVT1 is also exerted through direct interaction with phospho-STAT3, leading to protein stabilization and activation of the downstream pathway, resulting in VEGFA upregulation in gastric cancer [125].…”