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RNA sequencing of wild Type, Rictor-KO or GATA3-KO J774.1 cells

ABSTRACT: Purpose: Endosomal-lysosomal system is one of the pivotal degradation system for a varieties of extracellular substances, of which dysfunction has been indicated to be associated with cardiovascular and neurodegenerative diseases. This degradation process consists of multiple steps; uptake of extracellular molecules, endosomal formation and its transportation to lysosomes, and digestion by lysosomal enzymes. Whereas TFEB, is a transcriptional factor, has been well studied as a master regulator of cellular uptake and lysosomal function, a key regulatory mechanism for endosomal maturation remains unclear. We previously found that isorhamnetin, a dietary flavonoid, enhanced the endosomal-lysosomal proteolysis in J774.1 macrophage-like cell line, which was independent on mTORC1-TFEB axis. In this study, we analyzed the molecular mechanism of activated endosomal-lysosomal degradation by isorhamnetin.

ORGANISM(S): Mus musculus

PROVIDER: GSE167009 | GEO | 2022/02/15

REPOSITORIES: GEO

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A Lysosome independent role for TFEB in activating DNA repair and inhibiting apoptosis in breast cancer cells

Project description:Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy with critical roles in several cancers. Lysosomal autophagy promotes cancer survival through degradation of toxic molecules and maintenance of adequate nutrient supply. Doxorubicin (DOX) is the standard of care treatment for triple-negative breast cancer (TNBC); however, chemoresistance at lower doses and toxicity at higher doses limit its usefulness. By targeting pathways of survival, DOX can become an effective antitumor agent. In this study, we examined the role of TFEB in TNBC and its relationship with autophagy and DNA damage induced by DOX. In TNBC cells, TFEB was hypo-phosphorylated and localized to the nucleus upon DOX treatment. TFEB knockdown decreased the viability of TNBC cells while increasing caspase-3 dependent apoptosis. Additionally, inhibition of TFEB-phosphatase calcineurin sensitized cells to DOX-induced apoptosis in a TFEB dependent fashion. Regulation of apoptosis by TFEB was not a consequence of altered lysosomal function, as TFEB continued to protect against apoptosis in the presence of lysosomal inhibitors. RNA-Seq analysis of TFEB knockdown MDA-MB-231 cells identified a significant downregulation in cell cycle and homologous recombination while genes involved in interferon-γ and TNFα signaling were upregulated. In consequence, knockdown of TFEB was found to disrupt DNA repair following DOX, as evidenced by persistent γH2A.X detection. Together, these findings describe in TNBC a novel lysosomal independent function for TFEB in responding to DNA damage.

2020-12-22 | GSE139203 | GEO

HeLa-FLCN KO upon Trametinib treatment [Trametinib_RNAseq]

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Modulations of mTORC2-GATA3 is by isorhamnetin activates endosomal-lysosomal degradation in J774.1 macrophage-like cell line

Project description:Modulations of mTORC2-GATA3 is by isorhamnetin activates endosomal-lysosomal degradation in J774.1 macrophage-like cell line

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Transcription profiling of human EBV transformed cell lines established from patients with a novel immunodeficiency syndrome

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Stem cell fate choices are regulated through antagonistic control of lysosomes by MYC and TFEB [RNA-Seq 3]

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Stem cell fate choices are regulated through antagonistic control of lysosomes by MYC and TFEB [RNA-Seq 2]

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