Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2

Abstract

Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497 mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.

Up‐regulation of microRNA‐491‐5p suppresses cell proliferation and promotes apoptosis by targeting FOXP4 in human osteosarcoma

“…Several recently published studies have supported a role for microRNAs (miRNAs) in regulating fundamental normal and reactive cellular processes . Moreover, an increasing number of studies support a role for miRNA in the origination and progression of human cancers . Dysregulation of miRNA activity may result in progressive and uncontrolled tumour growth .…”

“…Previous studies have shown that 98 miRNAs are located at different genomic regions involved in human tumorigenesis, suggesting that miRNAs are involved in the development and pathogenesis of malignancies, and could possibly serve as diagnostic or prognostic tumour biomarkers . Furthermore, miRNAs play critical roles in a variety of other cellular processes, including tumour growth, cell apoptosis and tumour cell metastasis, and can act as either oncogenes or anti‐oncogenes . Additionally, the expression profiles of different miRNAs in plasma, serum and tumour samples have been used to accurately classify human cancers, suggesting that miRNAs could possibly serve as biomarkers for diagnosing human cancers and developing a prognosis for cancer patients …”

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

“…miRNAs are small (approximately 22 nucleotides in length), noncoding singlestranded RNA molecules that can regulate numerous biological processes, including cellular differentiation (Nolte-'t Hoen et al, 2015), proliferation (Zhao et al, 2012), apoptosis (Yeh et al, 2012), angiogenesis (Caporali and Emanueli, 2011), the development of cancer , and the inhibition of tumor angiogenesis and growth (Luo et al, 2013;Tu et al, 2015). Endometriosis is a common, although mysterious and fascinating, gynecological condition with diverse clinical manifestations and high variability.…”

MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

“…However, detailed information concerning the role of miR-497 in the development of atherosclerosis is unknown. Recent study has shown that miR-497 in HUVECs induce apoptosis and inhibit the proliferation via targeting VEGFR2/Raf/MEK/ERK signal pathway[13]. But that doesn’t represent it is the only way to affect the functions of ECs.…”