MiR-200c Increases the Radiosensitivity of Non-Small-Cell Lung Cancer Cell Line A549 by Targeting VEGF-VEGFR2 Pathway

Abstract

MicroRNAs (miRNAs) have been demonstrated to participate in many important cellular processes including radiosensitization. VEGF family, an important regulator of angiogenesis, also plays a crucial role in the regulation of cancer cell radiosensitivity. VEGFR2 mediates the major growth and permeability actions of VEGF in a paracrine/autocrine manner. MiR-200c, at the nexus of epithelial-mesenchymal transition (EMT), is predicted to target VEGFR2. The purpose of this study is to test the hypothesis that regulation of VEGFR2 pathway by miR-200c could modulate the radiosensitivity of cancer cells. Bioinformatic analysis, luciferase reporter assays and biochemical assays were carried out to validate VEGFR2 as a direct target of miR-200c. The radiosensitizing effects of miR-200c on A549 cells were determined by clonogenic assays. The downstream regulating mechanism of miR-200c was explored with western blotting assays, FCM, tube formation assays and migration assays. We identified VEGFR2 as a novel target of miR-200c. The ectopic miR-200c increased the radiosensitivity of A549 while miR-200c down-regulation decreased it. Besides, we proved that miR-200c radiosensitized A549 cells by targeting VEGF-VEGFR2 pathway specifically, thus leading to inhibition of its downstream pro-survival signaling transduction and angiogenesis, and serves as a potential target for radiosensitizition research.

Protease-activated Receptor-2 (PAR-2)-mediated Nf-κB Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma

“…miR-200c directly targets many pro-inflammatory genes, including IL-8, VEGFA, and VEGFR2. Additionally, miR-200c also targets IKK␤ (IKBKB), thereby decreasing Nf-B signaling and inhibiting scores of pro-inflammatory Nf-B-target genes (51)(52)(53). Furthermore, as let-7d, miR-23b, and miR200c are established tumor suppressor genes that are significantly down-regulated in OSCC, our data provide a potential mechanism whereby PAR-2 activation contributes to tumor progression (54 -61).…”

Downregulation of miR-329 promotes cell invasion by regulating BRD4 and predicts poor prognosis in hepatocellular carcinoma

“…Recently, emerging evidence reported that dysregulation of miRNAs may contribute to tumor development [18,19]. miRNAs, small noncoding RNAs, could regulate expression of the proteincoding genes [20][21][22]. It is already identified that miRNAs are related to cell apoptosis, prognosis, proliferation, and invasion [23,24].…”

Down-Regulation of miR-140 Induces EMT and Promotes Invasion by Targeting Slug in Esophageal Cancer

“…The major causes of death from cancer are complications arising from metastasis. microRNAs (miRNAs) have been reported to have critical regulatory roles in cancer biology [16,17,18]. Specifically for EC, it is already reported that miRNAs contributes to proliferation and invasion [19,20].…”