title: Identification of the lncRNA, AK156230, as a novel regulator of cellular senescence in mouse embryonic fibroblasts.
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.
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, P.R.China.|Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, P.R.China.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Chen
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, P.R.China.|Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, P.R.China.
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Cai
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, P.R.China.|Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, P.R.China.|Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, P.R.China.
authors.forename: Shun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, P.R.China.|Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, P.R.China.
authors.forename: Mei
authors.initials: M
authors.lastname: Meng
authors.affiliation: Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Xingcong
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Yang
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, P.R.China.|Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, P.R.China.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Dong
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, P.R.China.|Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, P.R.China.|Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, P.R.China.
authors.forename: Xinguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, P.R.China.|Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, P.R.China.|Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, P.R.China.|Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Xing-Dong
authors.initials: XD
authors.lastname: Xiong
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D062085:RNA, Long Noncoding / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; C000626067:long non-coding RNA AK156230, mouse
keywords: AK156230; Gerotarget; autophagy; cellular senescence; lncRNA; mouse embryonic fibroblasts