國家衛生研究院 NHRI:Item 3990099045/3939

NHRI > Institute of Cellular and Systems Medicine > Shan-Kung Lin(2004-2017) > Periodical Articles > Item 3990099045/3939

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Title:	A region within the 5'-untranslated region of hypoxia-inducible factor-1alpha mRNA mediates its turnover in lung adenocarcinoma cells
Other Titles:	A Region within the 5 '-Untranslated Region of Hypoxia-inducible Factor-1 alpha mRNA Mediates Its Turnover in Lung Adenocarcinoma Cells
Authors:	Wang, MJ;Lin, S
Contributors:	Institute of Cellular and Systems Medicine
Abstract:	Previously, we showed that CL1-5 cells express more hypoxia-inducible factor-1α (HIF-1α) than the parental CL1 cells, which bestows CL1-5 cells a stronger invasive activity. Here, we investigated the mechanisms underlying the differential expression of HIF-1α mRNA in CL1 and CL1-5 cells. Data showed that the transcription rate of HIF-1α gene in CL1 cells was slightly higher than that of CL1-5 cells, suggesting that the expression of HIF-1α mRNA in CL1 cells was repressed by post-transcriptional mechanisms. RNA electrophoretic mobility shift assays revealed a 61-base segment (designated as D5) within the 5′-untranslated repeat of HIF-1α mRNA, with which the CL1 cell lysates formed more prominent complexes (including complex I) than did CL1-5 cell lysates. Insertion of D5 into a reporter construct reduced the half-life of the chimeric transcripts in transfected CL1 but not CL1-5 cells; conversely, overexpression of D5-containing reporter construct in CL1 cells increased HIF-1α mRNA. We also identified the polypyrimidine tract-binding protein (PTB) as a required component of complex I. Deletion of the RNA recognition motif 1 (RRM1) or RRM3 of PTB abolished the formation of complex I. Our data showed that CL1 cells expressed more PTB than CL1-5 cells. Inhibition of PTB expression in CL1 cells decreased the formation of complex I, whereas overexpression of PTB in CL1-5 cells increased the levels of complex I, decreased the stability of HIF-1α and D5-containing chimeric mRNAs, and decreased cell invasiveness. In sum, we have identified in lung adenocarcinoma cells a mechanism that regulates HIF-1α expression by modulating HIF-1α mRNA stability.
Date:	2009-12-25
Relation:	Journal of Biological Chemistry. 2009 Dec 25;284(52):36500-36510.
Link to:	http://dx.doi.org/10.1074/jbc.M109.008904
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000272970500052
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=73649086216
Appears in Collections:	[Shan-Kung Lin(2004-2017)] Periodical Articles

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