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微小RNA-19a/b通过靶向肿瘤抑制因子MXD1来调控胃癌细胞的转移。

MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1.

作者信息

Wu Q, Yang Z, An Y, Hu H, Yin J, Zhang P, Nie Y, Wu K, Shi Y, Fan D

机构信息

State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

Cell Death Dis. 2014 Mar 27;5(3):e1144. doi: 10.1038/cddis.2014.110.

DOI:10.1038/cddis.2014.110
PMID:24675462
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3973221/
Abstract

The microRNAs 19a and 19b, hereafter collectively referred to as miR-19a/b, were recognised to be the most important miRNAs in the oncomiRs-miR-17-92 cluster. However, the exact roles of miR-19a/b in cancers have not been elucidated. In the present study, miR-19a/b was found to be over-expressed in gastric cancer tissues and significantly associated with the patients' metastasis of gastric cancer. Using gain or loss-of-function in in vitro and in vivo experiments, a pro-metastatic function of miR-19a/b was observed in gastric cancer. Furthermore, reporter gene assay and western blot showed that MXD1 is a direct target of miR-19a/b. Functional assays showed that not only MXD1 had an opposite effect to miR-19a/b in the regulation of gastric cancer cells, but also overexpression of MXD1 reduced both miR-19a/b and c-Myc levels, indicating a potential positive feedback loop among miR-19a/b, MXD1 and c-Myc. In conclusion, miR-17-92 cluster members miR-19a/b facilitated gastric cancer cell migration, invasion and metastasis through targeting the antagonist of c-Myc -- MXD1, implicating a novel mechanism for the malignant phenotypes of gastric cancer.

摘要

微小RNA 19a和19b（以下统称为miR-19a/b）被认为是致癌微小RNA-miR-17-92簇中最重要的微小RNA。然而，miR-19a/b在癌症中的确切作用尚未阐明。在本研究中，发现miR-19a/b在胃癌组织中过表达，且与胃癌患者的转移显著相关。通过体外和体内实验中的功能获得或功能丧失研究，观察到miR-19a/b在胃癌中具有促转移功能。此外，报告基因检测和蛋白质印迹表明MXD1是miR-19a/b的直接靶标。功能分析表明，不仅MXD1在调节胃癌细胞方面与miR-19a/b具有相反的作用，而且MXD1的过表达还降低了miR-19a/b和c-Myc的水平，表明在miR-19a/b、MXD1和c-Myc之间存在潜在的正反馈环。总之，miR-17-92簇成员miR-19a/b通过靶向c-Myc的拮抗剂MXD1促进胃癌细胞迁移、侵袭和转移，这为胃癌的恶性表型提供了一种新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e7/3973221/e148fe2c0d51/cddis2014110f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e7/3973221/c1306350b32e/cddis2014110f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e7/3973221/cb42482cf833/cddis2014110f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e7/3973221/cc5c13c632dd/cddis2014110f3.jpg
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