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Targeting FTO suppresses hepatocellular carcinoma by inhibiting ERBB3 and TUBB4A expression [RNA-seq]

ABSTRACT: Targeting FTO suppresses hepatocellular carcinoma by inhibiting ERBB3 and TUBB4A expression [RNA-seq]

PROVIDER: PRJNA1116222 | ENA |

REPOSITORIES: ENA

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Targeting FTO suppresses hepatocellular carcinoma by inhibiting ERBB3 and TUBB4A expression [MeRIP]

Project description:Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase and plays a critical oncogenic role in various cancers. Here we show that FTO is an effective target in hepatocellular carcinoma (HCC). FTO is highly expressed in clinical patients of HCC and presents as a poor prognostic factor. Genetic depletion of FTO dramatically attenuated HCC progression in vivo. Pharmacological inhibition of FTO by FB23/FB23-2 remarkably suppressed the proliferation and migration of HCC cell lines in vitro, as well as inhibiting the HCC tumorigenicity in xeno-transplanted mice. Mechanistically, FB23-2 suppressed the expression of Erb-b2 receptor tyrosine kinase 3 (ERBB3) and human tubulin beta class Iva (TUBB4A) by increasing the m6A level in these mRNA transcripts. The decreased ERBB3 resulted in inhibited Akt-mTOR signaling that subsequently impaired the proliferation and survival of HCC cells. Moreover, FB23-2 abolished the organization of the tubulin cytoskeleton, while enforced expression of TUBB4A rescued the migration of HCC cells. Collectively, our study demonstrated that FTO plays a critical role in HCC by maintaining the proliferation and migration of cells, and highlights the broad potential of FTO inhibitors for targeting HCC.

2025-01-03 | GSE268330 | GEO

Targeting FTO suppresses hepatocellular carcinoma by inhibiting ERBB3 and TUBB4A expression [MeRIP]

Project description:Targeting FTO suppresses hepatocellular carcinoma by inhibiting ERBB3 and TUBB4A expression [MeRIP]

| PRJNA1116226 | ENA

Targeting FTO suppresses hepatocellular carcinoma by inhibiting ERBB3 and TUBB4A expression [RNA-seq]

2025-01-03 | GSE268326 | GEO

FTO regulated genes in Hepatocellular Carcinoma

Project description:FTO regulated genes in Hepatocellular Carcinoma

| PRJNA631683 | ENA

Galectin-9 suppresses growth of hepatocellular carcinoma in vitro

Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in vitro study. Micro RNA expression of Li-7 cells, a cell line of hepatocellular carcinoma, with or without administration of galectin-9 were assessed in vitro.

2015-03-01 | E-GEOD-55665 | biostudies-arrayexpress

Galectin-9 suppresses growth of hepatocellular carcinoma in vivo

Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in xenograft model analysis. Micro RNA expression in xenografts of Li-7 cells, a cell line of hepatocellular carcinoma, with or without administration of galectin-9 were assessed.

2015-03-01 | E-GEOD-55666 | biostudies-arrayexpress

Quantitative Proteomics of Mouse Liver (FTO-KO,WT) in response to DEN injection

Project description:Single nucleotide polymorphisms in the FTO gene encoding a m6A demthylase are associated with obesity and cancer development. However, the functional role of FTO in the developemnt of progression of hepatocellular carcinoma (HCC) as a proteotypic obesity-associated cancer remains unclear. Here, we have generated mice with hepatic FTO deficiency (FTOL-KO) and subjected them to DEN induced HCC-development. FTOL-KO mice exhibit increased HCC burden. While control mice exhibit a dynamic regulation of FTO upon induction of liver damage, this response is abrogated in mice lacking FTO. Proteomic analyses revealed that liver damage-induced increases in FTO expression promotes m6A-demethylation of CUL4A reducing its protein expression. Functionally, knockdown of CUL4A restores the increased hepatocyte proliferation observed upon loss of FTO. Collectively, our study reveals a protective role for FTO-dependent dynamic m6A mRNA demethylation of CUL4A in the initiation of HCC development.

2020-11-03 | PXD018223 | Pride

FTO regulated genes in Hepatocellular Carcinoma

Project description:To investigate the global genes regulated by FTO high-throughput mRNA sequencing (RNA-Seq) was performed to compare the expression profile between HepG2 cells transfected with control siRNA or FTO siRNA.

2023-05-10 | GSE150260 | GEO

Targeted ErbB3 loss in mammary organoids harvested from ErbB3 DOX-KO mice +/- DOX treatment

2012-01-04 | GSE32129 | GEO

Targeted ErbB3 loss in mammary organoids harvested from ErbB3 DOX-KO mice +/- DOX treatment

Project description:Mammary organoids harvested from ErbB3 DOX-KO mice, which utilize MMTV-Cre transgene expression in the LE to cause genomic recombination at floxed ErbB3 alleles in ErbB3FL/FL were cultured in the presence or absence of doxycycline to induce ErbB3 loss. The gene expression shift following DOX-induced ErbB3 loss in the 3D organoids was examined by microarray. Gene expression patterns were interrogated in mammary organoids from ErbB3 inducible-knockout mice cultured in the presence of absence of doxycycline. Three biological replicates of the experiment were performed, resulting in a total of 6 samples (3 treatment, 3 control).

2012-01-04 | E-GEOD-32129 | biostudies-arrayexpress

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