HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis DOI Creative Commons
Dan Liu, Shanshan Lin,

Yueben Hu

et al.

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

Published: Dec. 23, 2024

Abstract Ferroptosis, an apoptosis-independent cell death pathway characterized by heightened lipid peroxidation, which holds promise for tumor suppression. Despite extensive research on long non-coding RNAs (LncRNAs) in ferroptosis, their role colorectal cancer (CRC) remains underexplored. We investigated the upregulation of AC145207.5 and HNRNPC expression CRC tissues through public dataset analysis in-house validation, identifying them as having significant diagnostic potential. In vitro experiments including MTS assay, transwell, colony formation, alongside in vivo studies using xenograft models, elucidated synergistic carcinogenic HNRNPC/AC145207.5 axis promoting malignant characteristics CRC. Mechanistically, m6A reader stabilized m6A-modified AC145207.5, contributing to its stabilization upregulation. Consequently, activated Nrf2/GPX4 axis, resulting increased GPX4 expression, inhibition GPX4-mediated facilitation progression. Our findings underscore clinical relevance illuminate regulatory suggesting implications targeted precision medicine

Language: Английский

Characterization of LINC00483 as a Novel Oncogene in Colorectal Cancer via Targeting miR‐601/TSPAN8 Signaling Axis DOI Open Access

Xiao Liu,

Hui Xiong, Tie Chen

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: March 1, 2025

LINC00483 is exerted a crucial function in many malignant tumors' progression, but the role of colorectal cancer (CRC) carcinogenesis remains not fully understood. The aim our study was to explore potential development CRC and its underlying molecular mechanism. In present study, level mRNA protein assessed through using qRT-PCR Western blot analysis assays. Cell proliferation by Counting Kit-8 (CCK-8) colony formation cell metastasis transwell Results revealed that elevated tissue lines. Upregulation negatively correlated with overall survival. expression tetraspanin 8 (TSPAN8) increased tissues, whereas miR-601 decreased, correlation between levels TSPAN8 positive, negative. deficiency could inhibit proliferation, migration, invasion Moreover, were inhibited lines after transfected mimics; this effect be eliminated overexpressed. also suggested N-cadherin decreased mimics, E-cadherin increased; abrogated overexpressed, which means mimics can CRC, cotransfection LINC00483, ability restored. conclusion, elucidated promote progression upregulating via sponging miR-601. This finding provided new drug target for treatment clinic.

Language: Английский

Citations

0
LncRNAs in oncogenic microenvironment: from threat to therapy DOI Creative Commons
Dipanjan Roy, B. Bhattacharya,

Rudra Chakravarti

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: March 13, 2025

LncRNAs are RNA molecules of more than 200 nucleotides in length and participate cellular metabolism responses through their diverse interactomedespite having no protein-coding capabilities. Such significant interactions also implicate the presence lncRNAs complex pathobiological pathways various diseases, affecting survival by modulating autophagy, inflammation apoptosis. Proliferating cells harbour a microenvironment that mainly stimulate growth-specific activities such as DNA replication, repair, protein synthesis. They recognise damages at macromolecular level, preventing them from reaching next-generation. have shown association with events occurring towards proliferation, regulating key dividing cells, dysregulation lncRNA transcriptome affects normal life-cycle, promoting development cancer. Furthermore, demonstrated an cancer growth progression governing cell growth, epithelial-mesenchymal transition metastasis. This makes attractive target for treatment can be used marker diagnosis prognosis diseases due to differential expression diseased samples. review delves into correlation fundamental signalling how this crosstalk shapes complexity oncogenic microhabitat.

Language: Английский

Citations

0
Integrative Transcriptomics Analysis Reveals Convergent Toxicological Effects of Perfluorooctanoic Acid and Perfluorooctane Sulfonate on Human Liver: Evidence from Multiple Models DOI Creative Commons
Renjun Yang, Nuoya Yin, Francesco Faiola

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 138112 - 138112

Published: April 1, 2025

Perfluorooctanoic acid and perfluorooctane sulfonate are well-known eight-carbon per- polyfluoroalkyl substances (8C-PFAS) potentially toxic for the human liver. However, direct experimental evidence demonstrating their toxicity on liver remains limited. Consequently, this study aimed to extrapolate 8C-PFAS mechanisms by leveraging omics data integrate mouse findings. Through integration analyses of nine datasets (one human, six murine, two rat), we identified 199 genes with known biological functions that commonly affected across species. We delineated a comprehensive regulatory network toxicity, may trigger fatty disease up-regulating CD36 PPARα pathway; dysregulate xenobiotic metabolism disrupting CAR CYP family genes; induce cancer dysregulating WNT, TGFβ, FGF21, P53 pathways. also ATF3, EGR1, ESR1, NFATC4, SNAI2, TP53, EZH2 as transcriptionally regulated 8C-PFAS, along PPARα, RXRα, FGFR1, TCF3, SMAD3 functionally impacted. Collectively, these factors account over 90 % 8C-PFAS-affected key genes. This not only developed novel method extrapolating risks integrating scattered based transcriptomics data, but proposes new which contributes cancer.

Language: Английский

Citations

0
HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis DOI Creative Commons
Dan Liu, Shanshan Lin,

Yueben Hu

et al.

Non-coding RNA Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis DOI Creative Commons
Junwen Qi, Tao Jiang, Bowen Liu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: April 15, 2025

Abstract Background Metastasis is a leading cause of colorectal cancer (CRC)-related mortality, yet its molecular mechanisms remain poorly understood. Long noncoding RNAs (lncRNAs) have emerged as critical regulators CRC metastasis, but their specific roles are not fully elucidated. This study identifies and characterizes novel lncRNA LINC02167 regulator metastasis. Methods expression was analyzed in tissues via real-time quantitative polymerase chain reaction fluorescence situ hybridization. Functional assays evaluated role cell migration, invasion, metastasis vitro vivo. Mechanistic exploration involves combination techniques, including RNA sequencing, mass spectrometry, pull-down, immunoprecipitation, chromatin luciferase reporter assays, stability bioinformatics analysis, to uncover the interactions pathways regulated by LINC02167. Results markedly upregulated strongly correlates with advanced clinical features poor prognosis. analyses reveal that enhances migration invasion promotes Mechanistically, serves scaffold, forming complex YBX1 ILF3 facilitate binding NSUN2-mediated m 5 C modification sites on KSR1 mRNA, thereby stabilizing mRNA activating ERK/MAPK signaling pathway drive Additionally, MYC-driven transcriptional activation leads upregulation CRC. Conclusions uncovers mechanism through which modification, underscoring potential promising therapeutic target for metastatic treatment.

Language: Английский

Citations

0
Harnessing Natural Inhibitors of Protein Synthesis for Cancer Therapy: A Comprehensive Review DOI Creative Commons
Liqin Liu, Zhihui Li, Wenshuang Wu

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 209, P. 107449 - 107449

Published: Oct. 4, 2024

Cancer treatment remains a formidable challenge in modern medicine, necessitating nuanced understanding of its molecular underpinnings and the identification novel therapeutic modalities. Among intricate web cellular pathways implicated oncogenesis, protein synthesis has emerged as fundamental process warranting meticulous investigation. This review elucidates multifaceted role tumor initiation progression, highlighting potential targeting key nodes within these viable strategies. Natural products have long served source bioactive compounds with owing to their structural diversity evolutionary honing. Within this framework, we provide thorough examination natural inhibitors promising candidates for cancer therapy, drawing upon recent advancements mechanistic insights. By synthesizing current evidence elucidating challenges opportunities, aims galvanize further research into development product-based anticancer therapeutics, thereby advancing clinical armamentarium against malignancies.

Language: Английский

Citations

0
HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis DOI Creative Commons
Dan Liu, Shanshan Lin,

Yueben Hu

et al.

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

Published: Dec. 23, 2024

Abstract Ferroptosis, an apoptosis-independent cell death pathway characterized by heightened lipid peroxidation, which holds promise for tumor suppression. Despite extensive research on long non-coding RNAs (LncRNAs) in ferroptosis, their role colorectal cancer (CRC) remains underexplored. We investigated the upregulation of AC145207.5 and HNRNPC expression CRC tissues through public dataset analysis in-house validation, identifying them as having significant diagnostic potential. In vitro experiments including MTS assay, transwell, colony formation, alongside in vivo studies using xenograft models, elucidated synergistic carcinogenic HNRNPC/AC145207.5 axis promoting malignant characteristics CRC. Mechanistically, m6A reader stabilized m6A-modified AC145207.5, contributing to its stabilization upregulation. Consequently, activated Nrf2/GPX4 axis, resulting increased GPX4 expression, inhibition GPX4-mediated facilitation progression. Our findings underscore clinical relevance illuminate regulatory suggesting implications targeted precision medicine

Language: Английский

Citations

0