Oncogene-Induced Senescence is Crucial Antitumor Defense Mechanism of Human Endometrial Stromal Cells DOI Open Access
А. Л. Торопов, Pavel I. Deryabin, Alla Shatrova

et al.

Published: July 26, 2023

Being the major cellular component of highly dynamic tissue endometrial stromal cells (EnSC) are exposed to cycles proliferation upon hormonal stimulation what might pose risks for mutations accumulation and malignization. However, tumors rare unusual types tumor. The present study aimed uncover defense mechanisms that underlie resistance EnSC against oncogenic transformation. All experiments were performed in vitro using following methods: FACS, WB, RT-PCR, IF, molecular cloning, lentiviral transduction, CRISPR/Cas9 genome editing. We revealed expression mutant HRASG12V results senescence EnSC. experimentally confirmed inability HRASG12V-expressing bypass resume even oestrogen stimulation. At level, induction oncogene-induced (OIS) was accompanied by activation MEK/ERK, PI3K/AKT, p53/p21WAF/CIP/Rb p38/p16INK4a/Rb pathways, however inhibiting either pathway did not prevent cell cycle arrest. PTEN loss established as additional feature HRASG12V-induced By CRISPR-Cas9 mediated knockout, we distinguished loss-induced a reserve mechanism transformation highlights an antitumor controlled multiple backup pathways.

Language: Английский

Oxidative Stress, Inflammation and Colorectal Cancer: An Overview DOI Creative Commons
Annamária Bardelčíková, Jindřich Šoltýs, Ján Mojžíš

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 901 - 901

Published: April 9, 2023

Colorectal cancer (CRC) represents the second leading cause of cancer-related deaths worldwide. The pathogenesis CRC is a complex multistep process. Among other factors, inflammation and oxidative stress (OS) have been reported to be involved in initiation development CRC. Although OS plays vital part life all organisms, its long-term effects on human body may different chronic diseases, including diseases. Chronic can lead oxidation biomolecules (nucleic acids, lipids proteins) or activation inflammatory signaling pathways, resulting several transcription factors dysregulation gene protein expression followed by tumor cell survival. In addition, it well known that intestinal diseases such as bowel disease (IBD) are associated with an increased risk cancer, link between IBD progression has reported. This review focuses role causative agent colorectal cancer.

Language: Английский

Citations

109

Mechanisms of sex differences in Alzheimer’s disease DOI Creative Commons
Chloe Lopez-Lee, Eileen Ruth S. Torres, Gillian Carling

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(8), P. 1208 - 1221

Published: Feb. 22, 2024

Alzheimer's disease (AD) and the mechanisms underlying its etiology progression are complex multifactorial. The higher AD risk in women may serve as a clue to better understand these complicated processes. In this review, we examine aspects of that demonstrate sex-dependent effects delve into potential biological responsible, compiling findings from advanced technologies such single-cell RNA sequencing, metabolomics, multi-omics analyses. We review evidence sex hormones chromosomes interact with various during aging, encompassing inflammation, metabolism, autophagy, leading unique characteristics between men women.

Language: Английский

Citations

88

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer DOI Creative Commons

Ruozhu Yang,

Yi Han,

Xinyu Guan

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 23, 2023

Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation hTERT, observed in over 90% tumors, plays significant role tumor initiation progression. An in-depth exploration hTERT mechanisms cancer holds promise advancing our understanding disease developing more effective treatment strategies. In breast cancer, expression is regulated by epigenetic, transcriptional, post-translational modification DNA variation. Besides its canonical function maintenance, exerts non-canonical roles that contribute to progression through telomerase-independent mechanisms. This comprehensive review summarizes regulatory governing elucidates functional implications activation. Given overexpression most cells, detection associated molecules are potential enhancing early screening prognostic evaluation cancer. Although still stages, therapeutic approaches targeting show viable strategies treatment. These methods also discussed this paper. Video Abstract.

Language: Английский

Citations

17

Pharmacotherapeutic Considerations on Telomere Biology: The Positive Effect of Pharmacologically Active Substances on Telomere Length DOI Open Access

Miruna-Maria Apetroaei,

Persefoni Fragkiadaki,

Bruno Ștefan Velescu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7694 - 7694

Published: July 13, 2024

Telomeres are part of chromatin structures containing repeated DNA sequences, which function as protective caps at the ends chromosomes and prevent degradation recombination, thus ensuring integrity genome. While telomere length (TL) can be genetically inherited, TL shortening has been associated with ageing multiple xenobiotics bioactive substances. characterised a reliable biomarker for predisposition to developing chronic pathologies their progression. This narrative review aims provide arguments in favour including measurements complex prognostic diagnostic panel importance assessing effect different pharmacologically active molecules on biology telomeres. Medicines used management cardiovascular diseases, diabetes, schizophrenia, hormone replacement therapy menopause, danazol, melatonin, probiotics have studied positive effects against shortening. All these classes drugs analysed present review, particular focus molecular mechanisms involved.

Language: Английский

Citations

7

Prostate Cancer and the Mevalonate Pathway DOI Open Access
Patricia Guerrero-Ochoa, Sergio Rodríguez-Zapater, Alberto Anel

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2152 - 2152

Published: Feb. 10, 2024

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to emergence of resistance mechanisms tumor employs when subjected monomolecular treatments. This review illustrates how dysregulation lipid metabolic pathway constitutes survival strategy adopted by tumors evade eradication efforts. Integrating this aspect into oncological management could prove valuable combating PCa.

Language: Английский

Citations

5

Upregulation of shelterin and CST genes and longer telomeres are associated with unfavorable prognostic characteristics in prostate cancer DOI
Gabriel Arantes dos Santos, Nayara Izabel Viana, Ruan Pimenta

et al.

Cancer Genetics, Journal Year: 2024, Volume and Issue: 284-285, P. 20 - 29

Published: March 16, 2024

Language: Английский

Citations

4

hTERT rs2735940 polymorphism influences lung cancer risk and overall survival in lung cancer patients undergoing platinum-based doublet chemotherapy DOI
Anjali Saini,

Heena Kansal,

Navneet Singh

et al.

Expert Review of Molecular Diagnostics, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

The hTERT gene is an essential part of the telomerase enzyme, preserving telomere length and encouraging cellular immortality. study aimed to investigate whether TERT SNP was associated with increased risk lung cancer in North Indian population. 387 patients undergoing platinum-based chemotherapy 384 healthy controls were genotyped for variant rs2735940 (T>C) using PCR-RFLP. determine significant association between genetic risk. Patients carrying homozygous mutant genotype (CC) showed a (0 R = 2.4, p 0.03). Furthermore, dominant model, combination (TC+CC) susceptibility AOR 1.67 (p 0.0016). For rs2735940, individuals SCLC significantly more likely develop 0.0004). Our results also that who received docetaxel cisplatin/carboplatin had better prognosis as compared alternative regimens. associates' toxicities polymorphism delivering insights improving biomarker development individualized treatment.

Language: Английский

Citations

0

Synergistic effect of cobalt ferrite-graphene oxide based hyperthermia and capsaicin to induce apoptosis and inhibit telomerase activity in breast cancer cells DOI

Seyed Ali Lajevardian,

Abbas Alibakhshi, Simzar Hosseinzadeh

et al.

Advances in Natural Sciences Nanoscience and Nanotechnology, Journal Year: 2024, Volume and Issue: 15(3), P. 035017 - 035017

Published: Aug. 30, 2024

Abstract Capsaicin is a bioactive phytochemical of red and chili peppers. It has shown therapeutic properties, including anticancer activities. In this study, the potential anti-telomerase effect capsaicin, as well synergic inhibitory compound in combination with cobalt ferrite-graphene oxide nanocomposites was investigated on breast cancer cell line. For purpose, ferrite/graphene (CoFe 2 O 4 /GO) nanoparticles were synthesized characterized. Then, different concentrations capsaicin CoFe /GO nanoparticles, their adenocarcinoma lines (MCF-7 MCF-10A) analyzed using MTT assay quantitative real-time PCR for assessing viability expression changes telomerase reverse transcriptase ( tert ), Bax Bcl2 genes, respectively. The results showed synergistic NPs MCF-7 that reduced IC50 value from 0.1 1 mg/ml to 0.05 0.5 mg ml −1 , Moreover, bcl genes decreased after treatment; while contrast, bax gene significantly increased. Consequently, treatment could induce apoptosis inhibit growth cells. conclusion, combinational be considered an efficient regimen cancer.

Language: Английский

Citations

3

The oncogenic lncRNA MIR503HG suppresses cellular senescence counteracting supraphysiological androgen treatment in prostate cancer DOI Creative Commons

Julia Kallenbach,

Mahdi Rasa,

Mehdi Heidari Horestani

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Dec. 16, 2024

Abstract Background The androgen receptor (AR), a ligand-dependent transcription factor, plays key role in regulating prostate cancer (PCa) growth. novel bipolar therapy (BAT) uses supraphysiological levels (SAL) that suppresses growth of PCa cells and induces cellular senescence functioning as tumor suppressive mechanism. long non-coding RNAs (lncRNAs) the regulation SAL-mediated remains unclear. This study focuses on SAL-repressed lncRNA MIR503HG , examining its involvement androgen-controlled PCa. Methods Transcriptome ChIP-Seq analyses treated with SAL were conducted to identify SAL-downregulated lncRNAs. Expression analyzed 691 patient samples, mouse xenograft tumors patient-derived xenografts. Knockdown overexpression experiments performed assess proliferation using senescence-associated β-Gal assays, qRT-PCRs, Western blotting. activity was confirmed spheroids. Results A large cohort analysis shows is overexpressed metastatic associated reduced survival, indicating potential oncogenic role. Notably, treatment expression across four different cell lines xenografts but interestingly not senescence-resistant LNCaP Abl EnzaR cells. Functional assays reveal promotes inhibits senescence, partly through miR-424-5p. Mechanistic rescue indicate regulates AKT-p70S6K p15 INK4b -pRb pathway. Reduced by or knockdown resulted decreased BRCA2 suggesting DNA repair mechanisms implications for PARP inhibitor sensitivity used BAT clinical trial. Conclusions acts an regulator repressing senescence. SAL-induced suppression enhances tumor-suppressive effects AR signaling, could serve biomarker responsiveness target combination therapies inhibitors.

Language: Английский

Citations

3

Establishment and characterization of a continuous goldfish muscle stem cell line for cell-cultured fish meat production DOI
Xue Ting, Hongwei Zheng,

Zhenxin Zhao

et al.

Aquaculture, Journal Year: 2025, Volume and Issue: unknown, P. 742599 - 742599

Published: April 1, 2025

Language: Английский

Citations

0