Dataset Information

VARS1 overexpression in hepatocellular carcinoma cell lines

ABSTRACT: VARS1 was transiently overexpressed in Hep3B and SNU-387 hepatocellular carcinoma-derived cell lines.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

SUBMITTER: Natalia Herman Sanchez

LAB HEAD: Manuel D. Gahete Ortiz

PROVIDER: PXD056392 | Pride | 2024-12-02

REPOSITORIES: Pride

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Source:

			Action	DRS
	20220906_SOL2022004_10_S2-A10_1_1109.d.quant	Other
	20220906_SOL2022004_11_S2-A11_1_1103.d.quant	Other
	20220906_SOL2022004_12_S2-A12_1_1089.d.quant	Other
	20220906_SOL2022004_13_S2-B1_1_1092.d.quant	Other
	20220906_SOL2022004_14_S2-B11_1_1105.d.quant	Other

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Project description:Alternative RNA splicing analysis in Hep3B cell cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen Hypoxia is a common characteristic of many solid tumors. The hypoxic microenvironment stabilizes hypoxia-inducible transcription factor 1? (HIF1?) and 2? (HIF2?) to activate gene transcription, which promotes tumor cell survival. 95% of human genes are alternatively spliced, producing RNA isoforms that code functionally distinct proteins. Thus, effective hypoxia response requires increased HIF target gene transcription as well as proper RNA splicing of these HIF target genes. However, it is unclear if and how hypoxia regulates RNA splicing of HIF target genes. This study determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF target genes in Hep3B cells and characterized the role of HIF in regulating AS of HIF induced genes. The results indicated that hypoxia generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion for hypoxia reduced genes. Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF target genes including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing reporters confirmed that transcriptional activation by HIF is sufficient to increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional activation of the PDK1 minigene by other transcription factor in the absence of endogenous HIF target gene activation fails to alter PDK1 RNA splicing, demonstrating a novel role of HIF target gene(s) in regulating RNA splicing of HIF target genes. Implications:This study demonstrates a novel function of HIF in regulating RNA splicing of HIF target genes. We analyzed total RNA from Hep3B cells cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Altanalyze software version 2.0.7. Techinical replicates were performed for Nx and Hx treated Hep3B cells

Dataset Information

VARS1 overexpression in hepatocellular carcinoma cell lines

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