Proteomics Identifies LUC7L3 as a Prognostic Biomarker for Hepatocellular Carcinoma DOI Creative Commons

Yushan Hou,

Siqi Wang, Yiming Zhang

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4004 - 4020

Published: April 27, 2024

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification facilitate precision medicine. We performed ssGSEA analysis quantify the pathway activity RNA three cohorts. Kaplan–Meier Cox methods were used survival analysis. GO GSEA analyze enrichment. confirmed that is significantly correlated prognosis, identified an alternative splicing-associated protein LUC7L3 as a potential prognostic biomarker. Further bioinformatics revealed high expression indicated more progressive subtype worse clinical features. Cell proliferation-related pathways enriched expression. Consistently, we proved knockdown could inhibit cell proliferation suppress activation associated signaling vitro. In this research, relevance between patient was outlined. Our newly provide stratification recurrence risk, facilitating early medical intervention before or disease progression.

Language: Английский

ENO1-Mediated Deoxycytidine Synthesis and Gemcitabine Resistance by Stabilizing RRM2 in Pancreatic Cancer DOI Creative Commons
Chao Yu, Hao Wang, Liwen Chen

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Pancreatic ductal adenocarcinoma is a highly malignant solid tumor of the digestive tract, and chemoresistance to gemcitabine an important cause shortened survival time in patients. Upregulation deoxypyrimidine synthesis one reasons for pancreatic cancer cells be resistant gemcitabine, however, specific mechanism leading increased still unclear. Ribonucleotide reductase M2 subunit (RRM2) overexpression through unclear mechanisms many types human significantly affects sensitivity various chemotherapy treatments. Here, we found that high expression enolase-1 (ENO1) closely related resistance Cellular experiments vivo confirmed ENO1 increases without relying on its glycolytic enzyme activity. Mechanistically, competitively binds RRM2 with ubiquitin E3 ligase STUB1, thereby weakening ubiquitination degradation by STUB1. This ENO1-mediated aggregation protein dNTPs cells, enhancing gemcitabine. Our study reveals novel role provides scientific basis development new therapeutic strategies targeting ENO1.

Language: Английский

Citations

0
Targeting Regulatory Noncoding RNAs in Human Cancer: The State of the Art in Clinical Trials DOI Creative Commons
Roberto Piergentili, Stefano Sechi

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 471 - 471

Published: April 4, 2025

Noncoding RNAs (ncRNAs) are a heterogeneous group of RNA molecules whose classification is mainly based on arbitrary criteria such as the molecule length, secondary structures, and cellular functions. A large fraction these ncRNAs play regulatory role regarding messenger (mRNAs) or other ncRNAs, creating an intracellular network cross-interactions that allow fine complex regulation gene expression. Altering balance between interactions may be sufficient to cause transition from health disease vice versa. This leads possibility intervening in mechanisms re-establish patients. The associated with all cancer hallmarks, proliferation, apoptosis, invasion, metastasis, genomic instability. Based function performed carcinogenesis, behave either oncogenes tumor suppressors. However, this distinction not rigid; some can fall into both classes depending tissue considered target molecule. Furthermore, them also involved regulating response traditional cancer-therapeutic approaches. In general, molecular by very still largely unclear, but it has enormous potential for development new therapies, especially cases where methods fail, their use novel more efficient biomarkers. Overall, review will provide brief overview human biology, specific focus describing most recent ongoing clinical trials (CT) which have been tested therapeutic agents evaluated

Language: Английский

Citations

0
p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7 DOI Creative Commons

Liangjie Sun,

Yi Li, Meng Wang

et al.

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: June 4, 2024

p53 deficiency plays a crucial role in chemotherapy resistance through various biological events, including posttranslational modifications (PTMs). Recently, lysine crotonylation (Kcr) has been shown to play vital cancer progression. However, the global p53-regulated crotonylome and function of these altered Kcr proteins after remain unclear. In this study, we used SILAC-based quantitative identify 3,520 1924 crotonylated response knockout. We found that increased RRM2 at K283 (RRM2K283Cr) presence promoted HCT116 cell cisplatin. discovered SIRT7 could be decrotonylase was downregulated knockout, resulting RRM2K283Cr. Mechanistically, inhibited apoptosis by upregulating protein expression RRM2K283Cr-mediated cleaved-PARP1 cleaved-caspase3 expression, upregulate upon deficiency. conclusion, our results indicated malignant colon cisplatin therapy regulating RRM2K283Cr expression. Our findings provide novel therapeutic target against p53-deficient cancer.

Language: Английский

Citations

3
Deciphering the Molecular Complexity of Hepatocellular Carcinoma: Unveiling Novel Biomarkers and Therapeutic Targets Through Advanced Bioinformatics Analysis DOI Creative Commons

Ata Moghimi,

Nasrin Bani Hosseinian,

Mahdi Mahdipour

et al.

Cancer Reports, Journal Year: 2024, Volume and Issue: 7(8)

Published: Aug. 1, 2024

ABSTRACT Background Hepatocellular carcinoma (HCC) represents a primary liver tumor characterized by bleak prognosis and elevated mortality rates, yet its precise molecular mechanisms have not been fully elucidated. This study uses advanced bioinformatics techniques to discern differentially expressed genes (DEGs) implicated in the pathogenesis of HCC. The objective is discover novel biomarkers potential therapeutic targets that can contribute advancement HCC research. Methods analysis this primarily utilized Gene Expression Omnibus (GEO) database as data source. Initially, Transcriptome console (TAC) screened for DEGs. Subsequently, we constructed protein–protein interaction (PPI) network proteins associated identified DEGs with STRING database. We obtained our hub using Cytoscape confirmed results through GEPIA Furthermore, assessed prognostic significance To explore regulatory interactions, miRNA‐gene was also constructed, incorporating information from miRDB For predicting impact gene overexpression on drug effects, CANCER DP. Results A comprehensive expression profiles revealed total 4716 DEGs, consisting 2430 upregulated 2313 downregulated sample compared healthy control group. These exhibited significant enrichment key pathways such PI3K‐Akt signaling pathway, nuclear receptors meta‐pathway, various metabolism‐related pathways. Further exploration PPI unveiled P53 pathway pyrimidine metabolism most prominent 10 ( ASPM , RRM2 CCNB1 KIF14 MKI67 SHCBP1 CENPF ANLN HMMR EZH2 ) upregulation samples Survival indicated levels these were strongly changes overall survival patients. Lastly, specific miRNAs found influence genes, providing valuable insights into underlying progression. Conclusion findings successfully pivotal discoveries significantly enhance understanding at level, opening new ways development targeted therapies improved evaluation.

Language: Английский

Citations

3
The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment DOI Creative Commons

Bisheng Cheng,

Lingfeng Li,

Yongxin Wu

et al.

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 15, 2023

Abstract Background Prostate cancer is a leading cause of cancer-related deaths among men worldwide. Docetaxel chemotherapy has proven effective in improving overall survival patients with castration-resistant prostate (CRPC), but drug resistance remains considerable clinical challenge. Methods We explored the role Ribonucleotide reductase subunit M2 (RRM2), gene associated senescence, sensitivity to docetaxel. evaluated RRM2 expression, docetaxel resistance, and ANXA1 expression cell lines tumour xenografts models. In addition, assessed impact knockdown, over-expression, PI3K/AKT pathway inhibition on cells Furthermore, we combination treatment COH29 Results Our results demonstrated positive association between tumor xenograft Knockdown increased docetaxel, suggesting its mediating resistance. observed that stabilizes ANXA1, which turn activates contributes Importantly, found resulted synergistic effect, further augmenting Conclusion findings suggest regulates by stabilizing ANXA1-mediated activation pathway. Targeting or may offer promising therapeutic strategy overcome cancer. Graphical

Language: Английский

Citations

9
Celastrol induces ferroptosis by suppressing RRM2 in hepatocellular carcinoma DOI Creative Commons
Xue Zhang, Man-Man Qi,

Kailun Huo

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(13), P. e33936 - e33936

Published: July 1, 2024

Language: Английский

Citations

2
Microglia in physiological conditions and the importance of understanding their homeostatic functions in the arcuate nucleus DOI Creative Commons
Mara A. Guzmán‐Ruiz,

Natalí N Guerrero Vargas,

Ricardo Jair Ramírez‐Carreto

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 4, 2024

Microglia are highly dynamic cells that have been mainly studied under pathological conditions. The present review discusses the possible implication of microglia as modulators neuronal electrical responses in physiological conditions and hypothesizes how these might modulate hypothalamic circuits health during obesity. Microglial diverse, depending on developmental stage brain region. evidence also suggests activity modulates microglial motility to control excitability. Additionally, we show expression genes associated with neuron-microglia interaction is down-regulated obese mice compared control-fed mice, suggesting an alteration contact-dependent mechanisms sustain arcuate-median eminence function. We discuss microglial-derived signals for excitability neurons homeostasis This emphasizes importance studying interplay between maintain proper circuit It aims elucidate disruptions normal activities can adversely affect health.

Language: Английский

Citations

2
A comparative study on the toxic effects of lead pollution and nanoplastic-lead mixed pollution on red drum and their detoxification strategies DOI
Zhicheng Sun, Linlin Zhao, Xin Peng

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 480, P. 136018 - 136018

Published: Oct. 2, 2024

Language: Английский

Citations

2
Activating Invasion and Metastasis in Small Cell Lung Cancer: Role of the Tumour Immune Microenvironment and Mechanisms of Vasculogenesis, Epithelial‐Mesenchymal Transition, Cell Migration, and Organ Tropism DOI Creative Commons
Carl He

Cancer Reports, Journal Year: 2024, Volume and Issue: 7(10)

Published: Oct. 1, 2024

Small cell lung cancer (SCLC) harbours the most aggressive phenotype of all cancers to correlate with its bleak prognosis. The aggression SCLC is partially attributable strong metastatic tendencies. biological processes facilitating metastasis in are still poorly understood and garnering a deeper understanding these may enable exploration additional targets against this hallmark treatment SCLC.

Language: Английский

Citations

2
A Review on Mitotane: A Target Therapy in Adrenocortical Carcinoma DOI Open Access
Fabiano Flauto, Maria Cristina De Martino,

Chiara Vitiello

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 4061 - 4061

Published: Dec. 4, 2024

Adrenocortical carcinomas (ACCs) are rare and aggressive malignancies of adrenal cortex, associated with largely unknown mechanisms biological development poor prognosis. Currently, mitotane is the sole approved drug for treating advanced adrenocortical being utilized more frequently as postoperative adjuvant therapy. Although it understood that targets cortex disrupts steroid production, its precise mechanism action requires further exploration. Additionally, affects cytochrome P450 enzymes, causes depolarization mitochondrial membranes, leads to an accumulation free cholesterol, ultimately resulting in cell death. Many patients treated develop disease progression over time, underlying need understand primary acquired resistance. In this manuscript, we provide overview on intracellular mitotane, exploring data regarding predictive factors response evidence resistance mechanisms. discussion, considered a real target

Language: Английский

Citations

2