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结直肠癌中 miR-490-3p 的表达降低预示着不良预后,并通过靶向 RAB14 促进细胞增殖和侵袭。

Decreased expression of miR‑490‑3p in colorectal cancer predicts poor prognosis and promotes cell proliferation and invasion by targeting RAB14.

机构信息

Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, P.R. China.

Department of General Surgery, First Hospital of Qinhuangdao, Hebei 066000, P.R. China.

出版信息

Int J Oncol. 2018 Sep;53(3):1247-1256. doi: 10.3892/ijo.2018.4444. Epub 2018 Jun 19.

DOI:10.3892/ijo.2018.4444
PMID:29916545
Abstract

Growing evidence indicates a potential role for miR‑490‑3p in tumorigenesis. However, its function in colorectal carcinoma (CRC) remains undefined. In this study, miR‑490‑3p was markedly downregulated in fifty colorectal cancer tissue samples compared with the corresponding adjacent non‑cancerous specimens, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of miR‑490‑3p were closely associated with tumor differentiation and distant metastasis. In addition, both Kaplan-Meier and multivariate analyses indicated CRC patients with elevated miR‑490‑3p amounts had prolonged overall survival. Overexpression of miR‑490‑3p markedly reduced proliferation, colony formation and invasion in CRC cells by enhancing apoptosis and promoting G2/M phase arrest. Furthermore, ectopic expression of miR‑490‑3p resulted in decreased expression of RAB14, which was directly targeted by miR‑490‑3p, as shown by the dual-luciferase reporter gene assay. Finally, in a nude mouse model, miR‑490‑3p overexpression significantly suppressed the growth of CRC cells. The above results indicated that miR‑490‑3p might constitute a prognostic indicator and a novel molecular target for miRNA-based CRC therapy.

摘要

越来越多的证据表明 miR-490-3p 在肿瘤发生中可能发挥作用。然而,其在结直肠癌(CRC)中的功能仍未确定。在本研究中,通过逆转录定量聚合酶链反应(RT-qPCR)发现,与相应的相邻非癌组织相比,五十例结直肠癌组织样本中 miR-490-3p 的表达明显下调。miR-490-3p 的表达水平与肿瘤分化和远处转移密切相关。此外,Kaplan-Meier 分析和多变量分析均表明,miR-490-3p 水平升高的 CRC 患者总生存期延长。过表达 miR-490-3p 通过增强细胞凋亡和促进 G2/M 期阻滞,显著降低 CRC 细胞的增殖、集落形成和侵袭能力。此外,双荧光素酶报告基因检测表明,miR-490-3p 的过表达导致 RAB14 表达下调,RAB14 是 miR-490-3p 的直接靶标。最后,在裸鼠模型中,miR-490-3p 的过表达显著抑制了 CRC 细胞的生长。上述结果表明,miR-490-3p 可能构成 CRC 预后指标和 miRNA 治疗 CRC 的新分子靶点。

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