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微小RNA-30a通过下调I型胰岛素样生长因子受体抑制结直肠癌转移。

MicroRNA-30a Inhibits Colorectal Cancer Metastasis Through Down-Regulation of Type I Insulin-Like Growth Factor Receptor.

作者信息

Liu Y C, Park Y R, Kim S L, Lee S T, Kim S W

机构信息

Department of Physiology, Chonbuk National University Medical School, Jeonju, Republic of Korea.

Department of Internal Medicine of Chonbuk, National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea.

出版信息

Dig Dis Sci. 2017 Nov;62(11):3040-3049. doi: 10.1007/s10620-017-4763-z. Epub 2017 Sep 20.

Abstract

BACKGROUND

miR-30a expression is down-regulated and regulates tumor suppressors in various cancers.

AIM

We investigated the mechanisms underlying the biological role of miR-30a in CRC.

METHODS

MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a.

RESULTS

miR-30a expression was significantly down-regulated in CRC tissues and in CRC tissue with lymph node metastasis compared to CRC tissue without metastasis. Overexpression of miR-30a suppressed migration and invasion through insulin-like growth factor 1 receptor (IGF1R) in CRC cells. miR-30a suppresses IGF1R protein expression and inhibits β-catenin or p-AKT and increases E-cadherin expression. The IGF1R expression level is also up-regulated in CRC tumors and inversely correlated with miR-30a in CRC specimens.

CONCLUSIONS

miR-30a functions as a tumor-suppressive miRNA, which may provide a therapeutic strategy for metastasis of CRC.

摘要

背景

miR-30a的表达下调,并在多种癌症中调节肿瘤抑制因子。

目的

我们研究了miR-30a在结直肠癌中发挥生物学作用的潜在机制。

方法

通过定量实时PCR和蛋白质印迹法分析微小RNA、信使核糖核酸和蛋白质的表达。采用伤口愈合试验、Transwell迁移和侵袭实验测定结直肠癌的迁移和侵袭能力。使用荧光素酶报告基因检测法来确认miR-30a的靶标。

结果

与无转移的结直肠癌组织相比,miR-30a在结直肠癌组织及伴有淋巴结转移的结直肠癌组织中的表达显著下调。miR-30a的过表达通过胰岛素样生长因子1受体(IGF1R)抑制结直肠癌细胞的迁移和侵袭。miR-30a抑制IGF1R蛋白表达,抑制β-连环蛋白或磷酸化AKT,并增加E-钙黏蛋白的表达。在结直肠癌肿瘤中IGF1R表达水平也上调,且在结直肠癌标本中与miR-30a呈负相关。

结论

miR-30a作为一种肿瘤抑制性微小RNA发挥作用,这可能为结直肠癌转移提供一种治疗策略。

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