Identification of the lncRNA, AK156230, as a novel regulator of cellular senescence in mouse embryonic fibroblasts

Yu Ning Chen, Meng Yun Cai, Shun Xu, Mei Meng, Xingcong Ren, Jay W. Yang, Yu Qi Dong, Xinguang Liu, Jin Ming Yang, Xing Dong Xiong

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Long noncoding RNAs (lncRNAs) have gained extensive attentions in recent years because of their potential importance in a variety of biological and pathological processes. In this study, we sought to explore the role of lncRNAs in cellular senescence. Here, we report that the lncRNA AK156230 was downregulated during replicative senescence in mouse embryonic fibroblasts (MEFs), and knockdown of AK156230 promotes a robust senescence phenotype, including increase in the numbers of the senescence-associated β-galactosidase-positive cells, decrease of cell proliferation, accumulation of cells in the G2/M phase and reduction of autophagic activity. The cells with knockdown AK156230 expression also exhibited increased levels of p21, p53 and phosphorylated p53, and a decreased activity of CDK1. Moreover, rapamycin-induced autophagy offered cytoprotective effect and rescued cellular senescence in AK156230 knockdown cells. Gene expression profile showed that the dysregulation of autophagy and cell cycle genes contributed to the induction of cellular senescence after AK1561230 silencing. Taken together, these results suggest that downregulation of AK156230 is involved in the induction of cellular senescence through its roles in autophagy and cell cycle progression. Our study identifies AK156230 as a critical lncRNA that has a role in regulating cellular senescence in MEFs.

Original languageEnglish (US)
Pages (from-to)52673-52684
Number of pages12
JournalOncotarget
Volume7
Issue number33
DOIs
StatePublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Oncology

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    Chen, Y. N., Cai, M. Y., Xu, S., Meng, M., Ren, X., Yang, J. W., Dong, Y. Q., Liu, X., Yang, J. M., & Xiong, X. D. (2016). Identification of the lncRNA, AK156230, as a novel regulator of cellular senescence in mouse embryonic fibroblasts. Oncotarget, 7(33), 52673-52684. https://doi.org/10.18632/oncotarget.10170