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下调 microRNA-183-5p 通过使 reticulocalbin-2/Wnt/β-catenin 信号通路失活来抑制结直肠癌细胞的增殖和侵袭。

Downregulation of microRNA‑183‑5p inhibits the proliferation and invasion of colorectal cancer cells by inactivating the reticulocalbin‑2/Wnt/β‑catenin signaling pathway.

机构信息

Department of Gastrointestinal Surgery, The Second People's Hospital of Lianyungang, Haizhou, Jiangsu 310000, P.R. China.

出版信息

Mol Med Rep. 2019 May;19(5):4475-4483. doi: 10.3892/mmr.2019.10059. Epub 2019 Mar 19.

Abstract

microRNAs (miRNAs) are frequently aberrantly expressed in colorectal cancer (CRC) and are considered to serve a critical role in the onset and development of CRC by binding to its target transcription factor. The aim of the present study was to examine the role of miRNA (miR)‑183‑5p in the proliferation, invasion and migration of CRC cells, in addition to its underlying mechanism. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the expression level of miR‑183‑5p. MTT and Transwell assays were performed to examine proliferation and invasion in SW620 cells. Western blot analysis was performed to determine the protein expression of reticulocalbin‑2 (RCN2), matrix metalloproteinase‑2, β‑catenin, cyclin D1 and c‑Myc. miR‑183‑5p expression was significantly upregulated in the CRC tissues compared with adjacent normal tissues. In addition, the inhibition of miR‑183‑5p suppressed proliferation, invasion and migration in SW620 cells. miR‑183‑5p downregulation or overexpression regulated the CRC cell cycle, invasion and migration by modulating RCN2 expression. Furthermore, the Wnt/β‑catenin pathway was observed to be involved in the inhibitory effect of miR‑183‑5p downregulation in CRC cell proliferation, invasion and migration. These results provided evidence that the downregulation of miR‑183‑5p inhibits CRC proliferation and invasion by regulating the RCN2/Wnt/β‑catenin pathway. miR‑183‑5p and RCN2 may serve an important role in the molecular etiology of CRC and have potential applications in CRC treatment.

摘要

微小 RNA(miRNA)在结直肠癌(CRC)中经常异常表达,被认为通过与靶转录因子结合在 CRC 的发生和发展中起关键作用。本研究旨在探讨 miRNA(miR)-183-5p 在 CRC 细胞增殖、侵袭和迁移中的作用及其潜在机制。逆转录-定量聚合酶链反应分析用于检测 miR-183-5p 的表达水平。MTT 和 Transwell 测定用于检测 SW620 细胞的增殖和侵袭。Western blot 分析用于确定网质蛋白 2(RCN2)、基质金属蛋白酶-2、β-连环蛋白、细胞周期蛋白 D1 和 c-Myc 的蛋白表达。与相邻正常组织相比,CRC 组织中 miR-183-5p 的表达明显上调。此外,抑制 miR-183-5p 抑制了 SW620 细胞的增殖、侵袭和迁移。miR-183-5p 的下调或过表达通过调节 RCN2 表达来调节 CRC 细胞周期、侵袭和迁移。此外,观察到 Wnt/β-连环蛋白通路参与了 miR-183-5p 下调对 CRC 细胞增殖、侵袭和迁移的抑制作用。这些结果表明,下调 miR-183-5p 通过调节 RCN2/Wnt/β-连环蛋白通路抑制 CRC 的增殖和侵袭。miR-183-5p 和 RCN2 可能在 CRC 的分子发病机制中起重要作用,并可能在 CRC 治疗中有应用前景。

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