Oncogenes and tumor suppressor genes: functions and roles in cancers

MedComm, Journal Year: 2024, Volume and Issue: 5(6)

Published: May 31, 2024

Abstract Cancer, being the most formidable ailment, has had a profound impact on human health. The disease is primarily associated with genetic mutations that oncogenes and tumor suppressor genes (TSGs). Recently, growing evidence have shown X‐linked TSGs specific role in cancer progression metastasis as well. Interestingly, our genome harbors around substantial portion of function suppressors, X chromosome alone considerable number TSGs. scenario becomes even more compelling are adaptive to key epigenetic processes such inactivation. Therefore, delineating new paradigm related TSGs, for instance, their crosstalk autosome involvement initiation, progression, utmost importance. Considering this, herein, we present comprehensive discussion TSG dysregulation various cancers consequence variations alterations. In addition, dynamic sex chromosome–autosome remodeling explored thoroughly. Besides, functional roles ncRNAs, immunomodulation gender‐based disparities also been highlighted. Overall, focal idea article recapitulate findings regulation landscape redefine toward improving treatment strategies.

Language: Английский

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Hypoxia-induced GPCPD1 depalmitoylation triggers mitophagy via regulating PRKN-mediated ubiquitination of VDAC1

Autophagy, Journal Year: 2023, Volume and Issue: 19(9), P. 2443 - 2463

Published: Feb. 20, 2023

Mitophagy, which selectively eliminates the dysfunctional and excess mitochondria by autophagy, is crucial for cellular homeostasis under stresses such as hypoxia. Dysregulation of mitophagy has been increasingly linked to many disorders including neurodegenerative disease cancer. Triple-negative breast cancer (TNBC), a highly aggressive subtype, reported be characterized However, role in hypoxic TNBC well underlying molecular mechanism largely unexplored. Here, we identified GPCPD1 (glycerophosphocholine phosphodiesterase 1), key enzyme choline metabolism, an essential mediator hypoxia-induced mitophagy. Under condition, found that was depalmitoylated LYPLA1, facilitated relocating outer mitochondrial membrane (OMM). Mitochondria-localized could bind VDAC1, substrate PRKN/PARKIN-dependent ubiquitination, thus interfering with oligomerization VDAC1. The increased monomer VDAC1 provided more anchor sites recruit PRKN-mediated polyubiquitination, consequently triggered In addition, GPCPD1-mediated exerted promotive effect on tumor growth metastasis both

Language: Английский

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LncRNA XIST regulates breast cancer stem cells by activating proinflammatory IL-6/STAT3 signaling

Oncogene, Journal Year: 2023, Volume and Issue: 42(18), P. 1419 - 1437

Published: March 15, 2023

Abstract Aberrant expression of XIST, a long noncoding RNA (lncRNA) initiating X chromosome inactivation (XCI) in early embryogenesis, is common feature breast cancer (BC). However, the roles post-XCI XIST carcinogenesis remain elusive. Here we identify as key regulator stem cells (CSCs), which exhibit aldehyde dehydrogenase positive (ALDH + ) epithelial- (E) and CD24 lo CD44 hi mesenchymal-like (M) phenotypes. variably expressed across spectrum BC subtypes, doxycycline (DOX)-inducible knockdown (KD) markedly inhibits spheroid/colony forming capacity, tumor growth tumor-initiating potential. This phenotype attributed to impaired E-CSC luminal E- M-CSC activities triple-negative (TN) BC. Gene profiling unveils that KD most significantly affects cytokine-cytokine receptor interactions, leading suppressed proinflammatory cytokines IL-6 IL-8 ALDH - bulk cells. Exogenous IL-6, but not IL-8, rescues reduced sphere-forming capacity proportion E-CSCs TN upon KD. functions nuclear sponge for microRNA let-7a-2-3p activate production from cells, acts paracrine fashion on display elevated cell surface (IL6R) expression. promotes CSC self-renewal via STAT3 activation factors including c-MYC, KLF4 SOX9. Together, this study supports novel role by derepressing let-7 controlled signaling promote self-renewal.

Language: Английский

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Long Non-Coding RNAs: Key Regulators of Tumor Epithelial/Mesenchymal Plasticity and Cancer Stemness

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 227 - 227

Published: Feb. 5, 2025

Long non-coding RNAs (lncRNAs) are a class of RNA molecules with transcripts longer than 200 bp, which were initially thought to be noise from genomic transcription without biological function. However, since the discovery H19 in 1980 and Xist 1990, increasing evidence has shown that lncRNAs regulate gene expression at epigenetic, transcriptional, post-transcriptional levels through specific regulatory actions involved development cancer other diseases. Despite many being expressed lower those protein-coding genes less sequence conservation across species, have become an intense area research. They exert diverse functions such as inducing chromatin remodeling, recruiting transcriptional machinery, acting competitive endogenous for microRNAs, modulating protein–protein interactions. Epithelial–mesenchymal transition (EMT) is developmental process, associated embryonic development, wound healing, progression. In context oncogenesis, EMT program transiently activated confers migratory/invasive stem cell (CSC) properties tumor cells, crucial malignant progression, metastasis, therapeutic resistance. Accumulating revealed play roles regulation epithelial/mesenchymal plasticity (EMP) stemness. Here, we summarize emerging molecular mechanisms regulating EMP their effects on initiation progression CSCs. We also discuss potential diagnostic prognostic biomarkers targets.

Language: Английский

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Escape from X inactivation is directly modulated by levels of Xist non-coding RNA

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 24, 2024

ABSTRACT In placental females, one copy of the two X chromosomes is largely silenced during a narrow developmental time window, in process mediated by non-coding RNA Xist 1 . Here, we demonstrate that can initiate X-chromosome inactivation (XCI) well beyond early embryogenesis. By modifying its endogenous level, show has capacity to actively silence genes escape XCI both neuronal progenitor cells (NPCs) and vivo , mouse embryos. We also plays direct role eliminating TAD-like structures associated with clusters escapee on inactive chromosome, this dependent Xist’s initiation partner, SPEN 2 further function suppressing gene expression escapees topological domain formation reversible for up seven days post-induction, but sustained up-regulation leads progressively irreversible silencing CpG island DNA methylation facultative escapees. Thus, distinctive transcriptional regulatory topologies chromosome actively, directly - reversibly controlled throughout life.

Language: Английский

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A genetic basis for sex differences in Xp11 translocation renal cell carcinoma

Cell, Journal Year: 2024, Volume and Issue: 187(20), P. 5735 - 5752.e25

Published: Aug. 20, 2024

Language: Английский

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Mechanisms of Long Non-Coding RNA in Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4538 - 4538

Published: Feb. 25, 2023

The landscape of pervasive transcription in eukaryotic genomes has made space for the identification thousands transcripts that are difficult to frame a specific functional category. A new class been broadly named as long non-coding RNAs (lncRNAs) and shortly defined longer than 200 nucleotides with no or limited coding potential. So far, about 19,000 lncRNAs genes have annotated human genome (Gencode 41), nearly matching number protein-coding genes. key scientific priority is characterization lncRNAs, major challenge molecular biology encouraged many high-throughput efforts. LncRNA studies stimulated by enormous clinical potential these molecules promise based on their expression mechanisms. In this review, we illustrate some mechanisms they pictured context breast cancer.

Language: Английский

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Mediator recruits the cohesin loader Scc2 to RNA Pol II-transcribed genes and promotes sister chromatid cohesion

Current Biology, Journal Year: 2022, Volume and Issue: 32(13), P. 2884 - 2896.e6

Published: June 1, 2022

The ring-like cohesin complex plays an essential role in chromosome segregation, organization, and double-strand break repair through its ability to bring two DNA double helices together. Scc2 (NIPBL humans) together with Scc4 functions as the loader of onto chromosomes. Chromatin adapters such RSC facilitate localization Scc2-Scc4 loader. Here, we identify a broad range Scc2-chromatin protein interactions that are evolutionarily conserved reveal for one complex, Mediator, recruitment We identified budding yeast Med14, subunit Mediator high copy suppressor poor growth mutant strains. Physical genetic between functionally substantiated direct cohesion assays. Depletion Med14 results defective sister chromatid decreased binding at RNA Pol II-transcribed genes. Previous work has suggested Nipbl, connect enhancers promoters active mammalian Our studies suggest fundamental

Language: Английский

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A novel human specific lncRNA MEK6-AS1 regulates adipogenesis and fatty acid biosynthesis by stabilizing MEK6 mRNA

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 8, 2025

Abstract Background Obesity is becoming one of the major non-communicable diseases with increasing incidence and risks that cannot be ignored. However effective safe clinical treatment strategies still need to deeply explored. Increased number volume adipocytes lead overweight obesity. The aim our work identify lncRNAs have important regulatory in differentiation human mesenchymal stem cells (MSCs) into adipocytes, provide targets for prevention obesity related metabolic disorders. Methods We extracted primary MSCs from adipose tissue, conducted expression profile analysis during adipogenic screen changed lncRNAs. Characteristics lncRNA were revealed mainly by RACE RNA FISH. Loss- gain-of function experiments vivo vitro used analyze effects lncRNA. Targeted metabolomics was utilized detect levels free fatty acids. pull-down, mRNA stability tests, etc. employed explore mechanisms Results Human-specific lncRNA, we named it MEK6-AS1, most up-regulated transcript MSCs. MEK6-AS1 highly expressed tissue samples individuals BMI ≥ 25 positively correlated marker genes these samples. Knocking down inhibited markers ectopic adipogenesis, reducing contents various acids, as well promoting osteogenic differentiation. Overexpression had opposite above processes. also found elevated hepatic steatosis organoid generation. Mechanistically, worked partially through stabilization MEK6 NAT10. Conclusions identified a human-specific (MEK6-AS1) position information genomic database but has not been extensively reported. demonstrated novel involved acid metabolism, may exert its effect enhancing Our study insights implication cell biology offer new potential therapeutic target other disease.

Language: Английский

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Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing

Nature Structural & Molecular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Language: Английский

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