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Effect of 14 hours of starvation on gene expression in the WM983B cell line using RNA-seq / Effect of HA15 resistance on gene expression in the WM983B cell line using RNA-seq

ABSTRACT: In order to examine the effect of starvation on gene expression and its contribution to the elevated ER stress, autophagy and apoptotic mechanisms we performed RNA-seq experiment on starved melanoma cells and on cells growing under normal cell conditions.The highest expression difference were seen for the RP11-134F2.8 gene (217 fold change) and the RP11-618G20.1 gene (64 fold change). Two starvation related genes including the SLCO4C1 (32 fold change), and PIK3IP1 (14 fold change) genes were also highly expressed in the starved WM983B cell population. We are the first who successfully established HA15 resistant melanoma cell lines (WM983BHA15RES) against 30uM HA15. In order to define gene expression alterations associated with the HA15 resistant phenotype we performed RNAseq analysis on the newly developed resistant melanoma cell line and compared the gene expression signature to the original WM983 cell line.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164261 | GEO | 2021/03/02

REPOSITORIES: GEO

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Project description:The lengthy and complicated multidrug therapy currently available to treat active tuberculosis (TB) infection has contributed to medical non-adherence and the emerging problems of multidrug-resistant (MDR)- and extensively drug-resistant (XDR)-TB, which are particularly deadly in the setting of HIV co-infection. The prolonged therapy required to eradicate TB infection is believed to reflect the ability of Mycobacterium tuberculosis (Mtb) to persist within host necrotic granulomas in a non-replicating state characterized by antibiotic tolerance to bactericidal drugs, which predominantly target actively dividing tubercle bacilli. The stringent response enzyme, RelMtb, is essential for Mtb survival under physiologically relevant stress conditions in vitro and in the lungs of mice and guinea pigs. A library of over 2 million compounds was screened in RelMtb-inhibition assays and whole-cell screens under conditions in which RelMtb is essential. A total of 178 RelMtb inhibitor candidates, representing 18 unique scaffolds, were identified and 39 compounds were tested against nutrient-starved wild-type Mtb. The antibiotic susceptibility of a relMtb deletion mutant (Δrel) was studied during nutrient starvation and chronic infection in mice, and isoniazid and RelMtb inhibitor candidates were tested for synergy against nutrient-starved wild-type Mtb and Δrel using checkerboard assays. The minimum bactericidal concentration of isoniazid was 500-fold lower against Δrel relative to wild type during nutrient starvation, and the potent bactericidal activity of isoniazid was maintained against Δrel during chronic infection in the lungs of mice. Inhibition of RelMtb appears to be a promising new approach to target Mtb persisters, with the potential to shorten the duration of treatment for drug-susceptible and drug-resistant TB. We used microarray to characterize the transcriptomic profiles of the wild type and Δrel during nutrient starvation. The RelMtb inhibitor, (E)-4-(3-methyl-4-(2-(4-methylthiazol-5-yl)ethoxy)styryl)benzoic acid, killed wild-type Mtb and prevented isoniazid tolerance during nutrient starvation. Treatment of nutrient-starved wild-type with the RelMtb inhibitor led to downregulation of the RelMtb regulon. Transcriptomic analysis revealed an altered gene expression in Δrel and wild-type treated with RelMtb inhibitor during nutrient starvation.

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Effect of 14 hours of starvation on gene expression in the WM983B cell line using RNA-seq / Effect of HA15 resistance on gene expression in the WM983B cell line using RNA-seq

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