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Mitochondrial RelA empowers mtDNA G-quadruplex formation for hypoxia adaptation in cancer cells

ABSTRACT: Mitochondrial DNA (mtDNA) G-quadruplexes (G4s) have been proposed as potential regulators of energy metabolism. However, numerous aspects of this process remain elusive. In our quest, employing a chemical-genetic screening strategy, we successfully identified the JAK/STAT3 pathway as the primary regulatory mechanism controlling mtDNA G4 dynamics in hypoxic MCF-7 cells. Further proteomic analyses and associated investigations have shed light on the translocation of RelA, a member of the NF-κB family, to the mitochondria upon activation of the JAK/STAT3 pathway. Once localized, RelA directly binds to mtDNA G4s and facilitates their folding, consequently yielding escalated mtDNA instability, impaired mtDNA transcription, and ensuing mitochondrial dysfunction. Ultimately, this intricately orchestrated cascade disrupts the equilibrium of energy metabolism, favoring a more pronounced deviation towards glycolysis. This pioneering revelation introduces an unprecedented and pivotal component to the intricately interconnected framework harnessed by cancer cells, empowering them to undergo metabolic reprogramming and adapt to hypoxic environments.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Tang Guixue

LAB HEAD: Tan Jiaheng

PROVIDER: PXD043639 | Pride | 2024-05-13

REPOSITORIES: Pride

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			Action	DRS
	H-C_1.raw	Raw
	H-C_2.raw	Raw
	H-C_3.raw	Raw
	H-R_1.raw	Raw
	H-R_2.raw	Raw

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Mouse livers during pneumonia

Project description:This SuperSeries is composed of the following subset Series: GSE32105: Expression data from mouse livers lacking STAT3 and RelA during pneumonia GSE35513: Expression data from mouse livers lacking NF-kappaB RelA (p65) during pneumonia GSE35514: Expression data from mouse livers lacking STAT3 during pneumonia GSE35515: Expression data from mouse livers expressing or lacking Cre recombinase during pneumonia Refer to individual Series

2012-02-16 | E-GEOD-35516 | biostudies-arrayexpress

Jak/Stat3 regulated global gene expression dynamics during late-stage reprogramming process

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Genome wide analysis of STAT3-mediated transcription and binding sites in mouse female germ stem cell (ChIP-seq)

Project description:Activation of JAK-STAT3 signaling by leukemia inhibitory factor (LIF) is required for maintaining self-renewal of mouse embryonic stem cells (mESCs). STAT3 perform cell type-specific roles in different cell type, here we revisit the role of STAT3 using mouse female germ stem cell (mFGSCs). We applied CRISPR/Cas9 system to generate Stat3 knockout FGSCs and then observed cell growth inhibition and cell cycle arrest in KO cell line. By combining genome wide ChIP-Seq and RNA-Seq, we identified 5990 STAT3 binding sites and discovered serval genes specific regulated by STAT3 that were involved in stem cell proliferation and female gonad development in FGSCs. In general, we identify key roles of STAT3 for sustains self-renewal and proliferation for FGSCs in this study.

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Expression data from mouse livers lacking STAT3 and RelA during pneumonia

Project description:A common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of two transcription factors, STAT3 and NF-kappaB p65 (RelA), on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia. Using the Cre-LoxP system, mice were generated with combined functional deletions of both STAT3 and RelA in hepatocytes. In mutant mice, Cre-recombinase was expressed under transcriptional control of an albumin promoter in the presence of homozygous floxed alleles for both STAT3 and RelA. Wild-type control mice lacked the Cre-recombinase transgene. Microarray analysis was performed on liver RNA collected from both genotypes of mice in the absence and presence of pneumococcal pneumonia. RNA from 4 separate groups of mice (3 mice per group) was analyzed: 1) Uninfected wild-type control mice; 2) Uninfected mutant mice lacking liver STAT3 and RelA; 3) Control mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3); and 4) Mutant mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3).

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Parallel G-quadruplexes recruit the HSV-1 transcription factor ICP4 to promote viral transcription in herpes virus-infected human cells

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