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静止期与衰老期差异表达基因的研究及 ARID5A 作为静止期相关标记物的鉴定

Differentially regulated gene expression in quiescence versus senescence and identification of ARID5A as a quiescence associated marker.

机构信息

Institute of Liver and Biliary Sciences, Vasant Kunj, Delhi, India.

Cedars-Sinai Advanced Health Sciences Pavilion, Los Angeles, California, USA.

出版信息

J Cell Physiol. 2018 May;233(5):3695-3712. doi: 10.1002/jcp.26227. Epub 2017 Dec 4.

Abstract

In multicellular organisms majority of the cells remain in a non-dividing states of either quiescence (reversible) or senescence (irreversible). In the present study, gene expression signatures unique to quiescence and senescence were identified using microarray in osteosarcoma cell line, U2OS. It was noted that certain genes and pathways like NOD pathway was shared by both the growth arrest conditions. A major highlight of the present study was increased expression of number of chemokines and cytokines in both quiescence and senescence. While senescence-associated secretory phenotype (SASP) is well known, the quiescence-associated secretory phenotype (QASP) is relatively unknown and appeared novel in this study. ARID5A, a subunit of SWI/SNF complex was identified as a quiescence associated gene. The endogenous expression of ARID5A increased during serum starved condition of quiescence. Overexpression of ARID5A resulted in more number of cells in G0/G1 phase of cell cycle. Further ARID5A overexpressing cells when subjected to serum starvation showed a pronounced secretory phenotype. Overall, the present work has identified gene expression signatures which can distinguish quiescence from senescence.

摘要

在多细胞生物中,大多数细胞处于非分裂状态,要么是静止(可逆),要么是衰老(不可逆)。在本研究中,使用微阵列在骨肉瘤细胞系 U2OS 中鉴定了静止和衰老特有的基因表达特征。值得注意的是,某些基因和途径,如 NOD 途径,在两种生长抑制条件下都有共享。本研究的一个主要亮点是在静止和衰老时,许多趋化因子和细胞因子的表达增加。虽然衰老相关分泌表型 (SASP) 是众所周知的,但静止相关分泌表型 (QASP) 相对未知,在本研究中似乎是新颖的。ARID5A 是 SWI/SNF 复合物的一个亚基,被鉴定为静止相关基因。在静止的血清饥饿条件下,ARID5A 的内源性表达增加。ARID5A 的过表达导致细胞周期 G0/G1 期的细胞数量增加。进一步的 ARID5A 过表达细胞在血清饥饿时表现出明显的分泌表型。总的来说,本工作鉴定了可以区分静止和衰老的基因表达特征。

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