The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1

Molecular Cancer
Chen-Hong DingWei-Fen Xie

Abstract

Our previous study has demonstrated that hepatocyte nuclear factor 1α (HNF1α) exerts potent therapeutic effects on hepatocellular carcinoma (HCC). However, the molecular mechanisms by which HNF1α reverses HCC malignancy need to be further elucidated. lncRNA microarray was performed to identify the long noncoding RNAs (lncRNAs) regulated by HNF1α. Chromatin immunoprecipitation and luciferase reporter assays were applied to clarify the mechanism of the transcriptional regulation of HNF1α to HNF1A antisense RNA 1 (HNF1A-AS1). The effect of HNF1A-AS1 on HCC malignancy was evaluated in vitro and in vivo. RNA pulldown, RNA-binding protein immunoprecipitation and the Bio-Layer Interferometry assay were used to validate the interaction of HNF1A-AS1 and Src homology region 2 domain-containing phosphatase 1 (SHP-1). HNF1α regulated the expression of a subset of lncRNAs in HCC cells. Among these lncRNAs, the expression levels of HNF1A-AS1 were notably correlated with HNF1α levels in HCC cells and human HCC tissues. HNF1α activated the transcription of HNF1A-AS1 by directly binding to its promoter region. HNF1A-AS1 inhibited the growth and the metastasis of HCC cells in vitro and in vivo. Moreover, knockdown of HNF1A-AS1 reversed the suppr...Continue Reading

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Citations

Jan 4, 2019·The Journal of Pharmacology and Experimental Therapeutics·Yiting WangLirong Zhang
Feb 27, 2020·Journal of Molecular Neuroscience : MN·Tayyeb BahramiMorteza Karimipoor
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Aug 19, 2021·Journal of Cellular and Molecular Medicine·Z L ZengJianghua Liu

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Datasets Mentioned

BETA
GSE103128

Methods Mentioned

BETA
xenografts
surgical resection
PCR
electrophoresis
immunoprecipitation
ChIP-PCR
transfection
pulldown
RIP
biosensors

Software Mentioned

GraphPad
Image
Pro Plus
Prism
BLAST
Gene Spring

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