miR-194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

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• 作者：Shun Xu ; Bing Zhang ; Yanmei Zhu ; Haijiao Huang ; Wenping Yang ; Haiyong Huang ; Hui-ling Zheng and Xinguang Liu
• 刊名：Cell Biology International
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：41
• 期：3
• 页码：249-257
• 全文大小：2966K
• ISSN：1095-8355

文摘

MicroRNA-194 (miR-194), a typical p53 responsive miRNA, serves as a tumor suppressor similar as p53, and has been demonstrated to play an anti-proliferation role in various human cancers. In spite of the pivotal role of p53 during aging process, the knowledge of miR-194's contribution to cellular senescence is limited. We herein sought to explore the role of miR-194 in the replicative senescence and stress-induced senescence of mouse embryonic fibroblasts. Our results unraveled that, compared to young cells, miR-194 is highly expressed in senescent cells, and extra expression of miR-194 significantly triggers the replicative senescence of MEFs and H₂O₂-induced senescence of NIH/3T3 cells, while inhibition of miR-194 exhibited the opposite effect. We further unveiled that DNMT3A was a direct and authentic target of miR-194, which has been reported to be closely associated with cellular senescence. Taken together, our data suggest that miR-194 may significantly promote the development of cellular senescence in mouse embryonic fibroblasts, which potentially occurs through inhibiting the DNMT3A expression.