Department of Gastroenterology, Department of Rehabilitative Medicine; Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6119-6130. doi: 10.26355/eurrev_201907_18425.
Previous studies have revealed that miR-511-5p was abnormally expressed in several cancers. In this study, we aimed to develop a study on the expression patterns, clinical value, and functional roles of miR-511-5p in colorectal cancer (CRC).
MiR-511-5p and GPR116 were analyzed in CRC cell lines and tumor specimens by Real-time PCR. The clinical correlations between miR-511-5p expression and the clinicopathologic factors and prognosis were analyzed. The potential influences of miR-511-5p expression on CRC cell growth, apoptosis, and invasion abilities were analyzed by MTT, clonogenic assay, flow cytometry and transwell assay, respectively. Luciferase assays, qRT-PCR and Western blotting were carried out for the discovery of the target gene of miR-511-5p.
MiR-511-5p was dramatically decreased in CRC samples and cells. Reduced miR-511-5p expressions were negatively correlated with histology/differentiation, invasion and TNM stage. Moreover, miR-511-5p was capable of being an independent prognostic predictor for CRC patients. It was also observed that overexpression of miR-511-5p depressed CRC cell growth and invasive abilities, and stimulated apoptosis. Mechanistically, we showed that miR-511-5p targeted the 3'-UTR of GPR116 and GPR116 reversed partial function of miR-511-5p in vitro.
MiR-511-5p may be used as a novel prognostic biomarker and functions as a novel anti-oncogene in CRC and the anti-oncogenic activity may involve its inhibition of the target gene GPR116.
先前的研究表明,miR-511-5p 在几种癌症中表达异常。本研究旨在探讨 miR-511-5p 在结直肠癌(CRC)中的表达模式、临床价值和功能作用。
通过实时 PCR 分析 CRC 细胞系和肿瘤标本中的 miR-511-5p 和 GPR116。分析 miR-511-5p 表达与临床病理因素和预后的临床相关性。通过 MTT、集落形成实验、流式细胞术和 Transwell 实验分别分析 miR-511-5p 表达对 CRC 细胞生长、凋亡和侵袭能力的潜在影响。通过荧光素酶报告实验、qRT-PCR 和 Western blot 检测 miR-511-5p 的靶基因。
miR-511-5p 在 CRC 样本和细胞中显著降低。降低的 miR-511-5p 表达与组织学/分化、侵袭和 TNM 分期呈负相关。此外,miR-511-5p 能够成为 CRC 患者的独立预后预测因子。研究还观察到,过表达 miR-511-5p 可抑制 CRC 细胞生长和侵袭能力,并促进细胞凋亡。机制上,我们表明 miR-511-5p 靶向 GPR116 的 3'UTR,GPR116 可逆转 miR-511-5p 在体外的部分功能。
miR-511-5p 可作为一种新的预后生物标志物,并在 CRC 中作为一种新的抑癌基因发挥作用,其抑癌活性可能涉及对靶基因 GPR116 的抑制。