Department of Gastroenterology, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):7963-7971. doi: 10.26355/eurrev_202008_22479.
The aim of this study is to explore the regulatory mechanism of circRNA UBAP2 (circUBAP2) in colorectal cancer (CRC).
The expression levels of circUBAP2, miR-199a, and VEGFA in tissues and cell lines were detected by RT-qPCR. The cell proliferation was examined by CCK-8 and colony formation assays. The migration and invasion abilities were evaluated by wound healing and transwell assays, respectively. Bioinformatics analysis and Luciferase activity assay were applied to determine the interaction between genes.
The expression of circUBAP2 was upregulated in CRC tissues and cell lines, and depletion of circUBAP2 suppressed the cell proliferation, migration, and invasion of CRC. Furthermore, miR-199a inhibitor abrogated the suppressive effect of circUBAP2 knockdown on CRC progression. Vascular endothelial growth factor A (VEGFA) was identified as a downstream target gene of miR-199a, and overexpression of VEGFA rescued the tumor phenotypes attenuated by circUBAP2 knockdown or miR-199a overexpression.
Our findings demonstrated that circUBAP2 facilitated CRC progression by sponging miR-199a to upregulate VEGFA. These findings implied that circUBAP2 may be a potential therapeutic biomarker for CRC.
本研究旨在探讨环状 RNA UBAP2(circUBAP2)在结直肠癌(CRC)中的调控机制。
采用 RT-qPCR 检测组织和细胞系中 circUBAP2、miR-199a 和 VEGFA 的表达水平。通过 CCK-8 和集落形成实验检测细胞增殖能力。通过划痕愈合和 Transwell 实验分别评估迁移和侵袭能力。通过生物信息学分析和荧光素酶活性测定来确定基因之间的相互作用。
circUBAP2 在 CRC 组织和细胞系中表达上调,circUBAP2 的耗竭抑制了 CRC 细胞的增殖、迁移和侵袭。此外,miR-199a 抑制剂消除了 circUBAP2 敲低对 CRC 进展的抑制作用。血管内皮生长因子 A(VEGFA)被鉴定为 miR-199a 的下游靶基因,并且 VEGFA 的过表达挽救了由 circUBAP2 敲低或 miR-199a 过表达减弱的肿瘤表型。
我们的研究结果表明,circUBAP2 通过海绵吸附 miR-199a 而上调 VEGFA 促进 CRC 进展。这些发现表明 circUBAP2 可能是 CRC 的潜在治疗生物标志物。