LncMAPK6 drives MAPK6 expression and liver TIC self-renewal

Journal of Experimental & Clinical Cancer Research : CR
Guanqun HuangZhixiang Jian

Abstract

Liver tumor initiating cells (TICs) have self-renewal and differentiate capacities, and largely contribute to tumor initiation, metastasis and drug resistance. MAPK signaling is a critical pathway in many biological processes, while its role in liver TICs hasn't been explored. Online-available dataset was used for unbiased screening. Liver TICs were examined CD133 FACS or oncosphere formation. TIC self-renewal was detected by oncosphere formation and tumor initiation assay. LncRNA function was detected by loss of function or gain of function assays. The molecular mechanism of lncRNA was explored by RNA pulldown, RNA immunoprecipitation, ChIP, western blot and double FISH. Here, we examined the expression profiles of MAPK components (MAPKs, MAP2Ks, MAP3Ks, MAP4Ks), and found MAPK6 is most highly expressed in liver cancer samples. Moreover, a divergent lncRNA (long noncoding RNA) of MAPK6, termed lncMAPK6 here, is also overexpressed along with liver tumorigenesis. LncMAPK6 promotes liver tumor propagation and TIC self-renewal through MAPK6. LncMAPK6 interacts with and recruits RNA polymerase II to MAPK6 promoter, and finally activates the transcription of MAPK6. Through MAPK6 transcriptional regulation, lncMAPK6 drives MARK signa...Continue Reading

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Citations

Jul 27, 2018·Journal of Experimental & Clinical Cancer Research : CR·Hui JiangXianhan Jiang
Dec 22, 2019·Journal of Experimental & Clinical Cancer Research : CR·Guanqun HuangZhixiang Jian
Jan 1, 2020·RNA Biology·Yan HuangXiangting Wang

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Datasets Mentioned

BETA
GSE14520

Methods Mentioned

BETA
xenograft
pulldown
PCR
immunoprecipitation
FACS

Software Mentioned

UCSC Genome Browser

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