miR-106b-25/miR-17-92簇在转化生长因子β信号调控中的新作用

Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling.

作者信息

Petrocca Fabio, Vecchione Andrea, Croce Carlo M

机构信息

Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.

出版信息

Cancer Res. 2008 Oct 15;68(20):8191-4. doi: 10.1158/0008-5472.CAN-08-1768.

DOI:10.1158/0008-5472.CAN-08-1768

PMID:18922889

Abstract

Inactivation of the transforming growth factor beta (TGFbeta) tumor suppressor pathway is a main step in the development of a variety of human tumors. The miR-106b-25 and miR-17-92 clusters are emerging as key modulators of TGFbeta signaling in gastrointestinal and other tumors, interfering with cell cycle arrest and apoptosis when overexpressed in cancer cells. Genetic ablation of these microRNAs (miRNAs) reveals their physiologic role in the control of liver and central nervous system apoptosis, supporting the notion that miRNA-based homeostatic mechanisms can be usurped by cancer cells to resist TGFbeta tumor suppression.

摘要

转化生长因子β（TGFβ）肿瘤抑制途径的失活是多种人类肿瘤发生发展的主要步骤。miR-106b-25和miR-17-92簇正成为胃肠道及其他肿瘤中TGFβ信号传导的关键调节因子，当在癌细胞中过表达时会干扰细胞周期停滞和细胞凋亡。对这些微小RNA（miRNA）进行基因敲除揭示了它们在控制肝脏和中枢神经系统细胞凋亡中的生理作用，支持了癌细胞可利用基于miRNA的稳态机制来抵抗TGFβ肿瘤抑制作用这一观点。