N6-methyladenosine-modified circRPS6KC1 regulated cell senescence in prostate cancer via FOXM1/PCNA axis DOI Creative Commons

Xuan Shu,

Jiahe Yi,

Jiangfeng Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Abstract Background Prostate cancer (PCa) gradually becomes the most common in men many countries, of which circRNAs and methylated modification exert an essential role prostate progression. However, concrete mechanism N6-methyladenosine (m6A) remains unclear. Methods circRNA-seq bioinformatic analysis reveal novel up-regulated circRPS6KC1 PCa. Function experiments vitro vivo, such as colony formation assay, cell counting kit-8 cycle analysis, EdU assays, senescence associated β-galactosidase staining subcutaneous xenograft tumor models, were conducted to show effect on senescence. RNA Immunoprecipitation (RIP), (MeRIP), pull-down, chromatin immunoprecipitation (ChIP) dual-luciferase reporter assays performed explore regulatory mechanism. Results We identified a circRNA, circRPS6KC1, was significantly cells clinical tissues. METTL3/YTHDF1 participated m6A stabilized it. Suppression contributed cancer. Mechanically, acted miR-761 sponge regulate FOXM1 expression. mediated transcription PCNA influenced p21 degradation, resulted up-regulation induced p53-independent manner. Conclusion by regulated via FOXM1/PCNA axis

Language: Английский

N6-methyladenosine-modified circRPS6KC1 regulated cellular senescence in prostate cancer via FOXM1/PCNA axis DOI

Xuan Shu,

Jiahe Yi,

Jiangfeng Li

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 125, P. 111510 - 111510

Published: Nov. 15, 2024

Language: Английский

Citations

1
The Annexin A1 Protein Mimetic Peptide Ac2‐26 prevents cellular senescence of CHON‐001 chondrocytes against tumor necrosis factor‐α via the Nrf2/NF‐κB pathway DOI Open Access
Lei Yang,

K GONG,

Guosheng Ren

et al.

Biotechnology and Applied Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Osteoarthritis (OA) is a degenerative joint disorder characterized by progressive cartilage degradation. Excessive oxidative stress (OS), inflammatory responses, extracellular matrix breakdown, and cellular senescence of chondrocytes play crucial roles in the pathological development OA. Currently, curing OA remains significant challenge. In this study, we aimed to elucidate protective effects Annexin A1 protein Mimetic Peptide (Ac2-26) against tumor necrosis factor-α (TNF-α)-induced damage CHON-001 assessing senescence, OS, expression levels metalloproteinase-13 (MMP-13) disintegrin metalloproteinase with thrombospondin motifs (ADAMTS)-4. Our results show that Ac2-26 mitigated reduction telomerase activity exacerbation induced TNF-α chondrocytes. Treatment led decreased human reverse transcriptase gene increased telomeric repeat-binding factor 2 gene, which were reversed treatment. The TNF-α-induced increases expressions p53 p16 restored dose-dependent manner. Additionally, found caused elevations mRNA MMP-13 ADAMTS-4, reduced fashion. Furthermore, triggered activation nuclear κ-B (NF-κB) increasing phosphorylated NF-κB p65 luciferase NF-κB. Notably, alleviated OS reducing mitochondrial reactive oxygen species promoting NF-E2-related (Nrf2) TNF-α-challenged Silencing Nrf2 abolished Ac2-26-induced Collectively, these findings offer new insights into potential therapeutic use for treating

Language: Английский

Citations

1
Functional circuits of LYL1 controlled by supraphysiological androgen in prostate cancer cells to regulate cell senescence DOI Creative Commons

Mehdi Heidari Horestani,

Katrin Schindler,

Aria Baniahmad

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 12, 2024

Abstract Background Prostate cancer (PCa) is a public health problem mostly reported in developed countries. The androgen receptor (AR) regulates the development and physiological function of normal prostate as well proliferation cancerous tissue. Treatment with supraphysiological levels (SAL) used bipolar therapy inhibits PCa growth, suggesting SAL induces tumor suppressive program. It was shown that cellular senescence, cell lines, human samples xenografted mouse model. Methods Transcriptome ChIP-seq analysis, spheroids, knockdown (KD), co-immunoprecipitation, qRT-PCR, immune detection, situ histochemistry. Results Here we show LYL1 upregulated by clock gene BHLHE40 both C4-2 LNCaP cells mediates SAL-induced senescence. transcriptional co-factor oncogenic activity leukemia. However, analysis large cohort patients shows expression reduced during significantly associated overall survival. through upregulation BHLHE40. On other hand, KD enhances via negative feedback loop including p27kip1. Regulatory loops were identified rescue experiments. Functional revealed reduces whereas p27kip1 levels. suggests this cycle inhibitor mediator senescence - regulatory loop. Interestingly, data recruitment AR to indicating novel direct target factors. Furthermore, RNA-seq from encompass overlap genes co-regulatory controlled androgens. In line this, co-immunoprecipitation complex AR. Conclusions Three feed-back AR- / -p27kip1 axis has been mediating cells. Graphical

Language: Английский

Citations

1
Cellular senescence: A potential mode of circular RNAs regulating prostate cancer DOI Creative Commons
Yunpeng Li, Aoyu Fan, Yunyan Zhang

et al.

MedComm – Oncology, Journal Year: 2023, Volume and Issue: 2(4)

Published: Dec. 1, 2023

Abstract Cellular senescence is a state characterized by permanent cell cycle stoppage, which has long been viewed as protective mechanism against neoplasia. However, accumulating evidence reveal that cellular variously stimulates tumorigenesis and malignant progression in certain contexts. Senescence‐associated secretory phenotype (SASP) crucial feature of senescent cells the main way they function. Prostate cancer (PCa) apparently an age‐related tumor with high prevalence elderly. With aggravation population aging morbidity PCa continues to rise. And progress disease, most patients eventually develop castration‐resistant (CRPC) or drug resistance, poses challenge for treatment aggravates burden on society. Circular RNAs (circRNAs) are class endogenous noncoding formed back‐splicing pre‐mRNAs. Characterized special covalently closed circular structure, play important regulatory roles various tumors. Numerous studies have revealed circRNAs can regulate diverse ways. This review explores potential mode PCa, reveales significant suggesting new strategy research.

Language: Английский

Citations

2
N6-methyladenosine-modified circRPS6KC1 regulated cell senescence in prostate cancer via FOXM1/PCNA axis DOI Creative Commons

Xuan Shu,

Jiahe Yi,

Jiangfeng Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Abstract Background Prostate cancer (PCa) gradually becomes the most common in men many countries, of which circRNAs and methylated modification exert an essential role prostate progression. However, concrete mechanism N6-methyladenosine (m6A) remains unclear. Methods circRNA-seq bioinformatic analysis reveal novel up-regulated circRPS6KC1 PCa. Function experiments vitro vivo, such as colony formation assay, cell counting kit-8 cycle analysis, EdU assays, senescence associated β-galactosidase staining subcutaneous xenograft tumor models, were conducted to show effect on senescence. RNA Immunoprecipitation (RIP), (MeRIP), pull-down, chromatin immunoprecipitation (ChIP) dual-luciferase reporter assays performed explore regulatory mechanism. Results We identified a circRNA, circRPS6KC1, was significantly cells clinical tissues. METTL3/YTHDF1 participated m6A stabilized it. Suppression contributed cancer. Mechanically, acted miR-761 sponge regulate FOXM1 expression. mediated transcription PCNA influenced p21 degradation, resulted up-regulation induced p53-independent manner. Conclusion by regulated via FOXM1/PCNA axis

Language: Английский

Citations

0