FOXO1 regulates expression of a microRNA cluster on X chromosome.
FOXO1 regulates expression of a microRNA cluster on X chromosome.
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DOI:
10.18632/aging.100558
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发表时间:
2013-05
期刊:
影响因子:
--
通讯作者:
Kandel ES
中科院分区:
文献类型:
--
作者:
Singhal R;Bard JE;Nowak NJ;Buck MJ;Kandel ES
Phosphoinositol-3-kinase (PI3K) pathway is a crucial modulator of many physiological and pathophysiological phenomena, including aging, diabetes and cancer. Protein kinase Akt, a downstream effector of PI3K, controls a plethora of cellular functions, including gene transcription. A key mechanism connecting Akt activity to changes in gene expression is inhibitory phosphorylation of FOXO family of transcription factors. Accordingly, altered expression of FOXO targets may account for many biological consequences of PI3K/Akt signaling. While the previous efforts focused on FOXO-dependent regulation of protein-coding genes, non-coding RNA genes have emerged as equally important targets of many transcription factors. Therefore, we utilized a regulated form of FOXO1 to profile FOXO1-dependent changes in miRNA expression in human cells. Both microarray hybridization and next-generation sequencing revealed changes in the products of a miRNA cluster on X chromosome. Rapid induction of these miRNAs occurred independently of de novo protein synthesis. Furthermore, inhibition of PI3K in cancer cell lines caused derepression of these miRNAs, as would be expected for FOXO-regulated genes. Members of the major oncogenic cascades are significantly overrepresented among the predicted targets of the miRNAs, consistent with tumor-suppressive role of FOXO1. The discovered miRNAs represent new candidate mediators of FOXO1 functions and possible biomarkers of its activity.
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影响因子:
3.7
作者:
Corcoran DL;Pandit KV;Gordon B;Bhattacharjee A;Kaminski N;Benos PV
通讯作者:
Benos PV
影响因子:
9.9
作者:
Eijkelenboom, Astrid;Mokry, Michal;Burgering, Boudewijn M. T.
通讯作者:
Burgering, Boudewijn M. T.
DOI:
10.1007/bf02674280
发表时间:
1997-09-01
期刊:
SOMATIC CELL AND MOLECULAR GENETICS
影响因子:
--
作者:
Kandel, ES;Chang, BD;Roninson, IB
通讯作者:
Roninson, IB
影响因子:
14.9
作者:
LITTLEWOOD, TD;HANCOCK, DC;EVEN, GI
通讯作者:
EVEN, GI
影响因子:
64.5
作者:
Lewis, BP;Shih, IH;Burge, CB
通讯作者:
Burge, CB