Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes DOI Creative Commons
Ovais Shafi,

Rahimeen Rajpar,

Shakaib Zafar

et al.

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

Published: May 7, 2024

Abstract Background: Hepatocellular carcinoma (HCC) presents challenges due to tumor heterogeneity and therapeutic resistance. Understanding the molecular mechanisms driving is crucial. Key transcription factors (HNF4A, HNF1A, FOXA1/2, etc.) signaling pathways (Wnt/β-catenin, FGF, HGF, are dysregulated in HCC. Dysregulation disrupts hepatocyte genetic programming, leading heterogeneous cell populations. Investigating these offers insights for targeted therapies improving patient outcomes Methods: Databases, including PubMed, MEDLINE, Google Scholar, open access/ subscription-based journals were searched published articles without any date restrictions, trace emergence of HCC by investigating hepatocyte-specific genes/TFs/signaling across cellular landscapes. Based on criteria mentioned methods section, studies systematically reviewed investigate Heterogeneity. This study adheres relevant PRISMA guidelines (Preferred Reporting Items Systematic Reviews Meta-Analyses). Results: into hepatocellular revealed dysregulation key (TFs) pathways. Transcription HNF4A, CEBPA, GATA4/6, PROX1, SOX9, HNF6/Onecut1, ONECUT2/HNF6β showed altered expression patterns, disrupting programming promoting populations Dysregulated Wnt/β-catenin, TGF-β, Hippo influenced fate decisions interactions with microenvironment, further contributing heterogeneity. NOTCH TBX3/18 highlighted complexity points critical role TFs transdifferentiation, providing interventions improve outcomes. Conclusion: The decline gene type-specific genes dysregulates programing hepatocytes involved homeostasis. multiple roles every gene/TF begin manifest themselves causing homeostasis, transdifferentiation. like along such as Wnt/β-catenin signaling, play crucial roles. disruption sets stage diverse phenotypes within microenvironment. vital developing strategies address

Language: Английский

Comprehensive RNA-Seq Gene Co-Expression Analysis Reveals Consistent Molecular Pathways in Hepatocellular Carcinoma across Diverse Risk Factors DOI Creative Commons

Nicholas Dale D. Talubo,

Po‐Wei Tsai, Lemmuel L. Tayo

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 765 - 765

Published: Sept. 26, 2024

Hepatocellular carcinoma (HCC) has the highest mortality rate and is most frequent of liver cancers. The heterogeneity HCC in its etiology molecular expression increases difficulty identifying possible treatments. To elucidate mechanisms across grades, data from Cancer Genome Atlas (TCGA) were used for gene co-expression analysis, categorizing each sample into pre-existing risk factors. R library BioNERO was preprocessing network construction. For those modules correlated with a grade, functional enrichments different databases then tested, which appeared to have relatively consistent patterns when grouped by G1/G2 G3/G4. exhibited involvement pathways related metabolism PI3K/Akt pathway, regulates cell proliferation pathways, whereas G3/G4 showed activation adhesion genes p53 signaling apoptosis, cycle arrest, similar processes. Module preservation analysis no history dataset as reference network, found molecules be preserved all factors, suggesting they are imperative development regardless potential etiology. Through hierarchical clustering, cycle, adhesion, immune system, ribosome consistently present distinct clusters linked oxidative phosphorylation viral pentose glucuronate interconversions non-viral HCC, underscoring their roles cancer progression.

Language: Английский

Citations

1
Withaferin-A induced Vimentin S56 phosphorylation dissociates NEDD9 signaling loop to regress progressive metastatic melanoma into lung adenocarcinoma. DOI

Ankith Sherapura,

Bayram Kıran,

G.S. Pavan Kumar

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: unknown, P. 111319 - 111319

Published: Nov. 1, 2024

Language: Английский

Citations

1
Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma DOI
Junling Yang, Jie Yang,

Rong-Fei Fang

et al.

World Journal of Hepatology, Journal Year: 2024, Volume and Issue: 16(12), P. 1480 - 1492

Published: Nov. 29, 2024

BACKGROUND Angiopoietin-2 (Ang-2) level is related to hepatocellular carcinoma (HCC) progression. However, the dynamic expression and regulatory mechanism of Ang-2 remain unclear. AIM To investigate levels in chronic liver diseases validate early monitoring value with a model hepatocarcinogenesis. METHODS Sprague-Dawley rats hepatocarcinogenesis were induced diet 2-fluorenylacet-amide, grouped based on histopathology by hematoxylin eosin staining. Differently expressed genes or mRNA livers analyzed whole-genome microarray. detected an enzyme-linked immunosorbent assay. RESULTS Clinical observation reveled that circulating hypoxia-inducible factor-1α (HIF-1α) patients progressively increased from benign HCC (P < 0.001). Dynamic validated up-regulated blood was positively correlated HIF-1α Mechanistically, regulated HIF-1α. When specific HIF-1α- microRNAs transfected into cells, cell proliferation significantly inhibited, down-regulated, also affected epithelial-mesenchymal transition via increasing E-cadherin block invasion migration reducing snail, twist vimentin. CONCLUSION Hypoxia-induced up-regulating might serve as sensitive biomarker for metastasis.

Language: Английский

Citations

1
Enhancing the Interactions of Ion-Tagged Oligonucleotides and Magnetic Ionic Liquid Supports for the Sequence-Specific Extraction of Hepatitis B Virus DNA DOI
Seong-Soo Lee, Derek R. Eitzmann, Jared L. Anderson

et al.

Analytica Chimica Acta, Journal Year: 2024, Volume and Issue: 1338, P. 343563 - 343563

Published: Dec. 18, 2024

Language: Английский

Citations

1
Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes DOI Creative Commons
Ovais Shafi,

Rahimeen Rajpar,

Shakaib Zafar

et al.

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

Published: May 7, 2024

Abstract Background: Hepatocellular carcinoma (HCC) presents challenges due to tumor heterogeneity and therapeutic resistance. Understanding the molecular mechanisms driving is crucial. Key transcription factors (HNF4A, HNF1A, FOXA1/2, etc.) signaling pathways (Wnt/β-catenin, FGF, HGF, are dysregulated in HCC. Dysregulation disrupts hepatocyte genetic programming, leading heterogeneous cell populations. Investigating these offers insights for targeted therapies improving patient outcomes Methods: Databases, including PubMed, MEDLINE, Google Scholar, open access/ subscription-based journals were searched published articles without any date restrictions, trace emergence of HCC by investigating hepatocyte-specific genes/TFs/signaling across cellular landscapes. Based on criteria mentioned methods section, studies systematically reviewed investigate Heterogeneity. This study adheres relevant PRISMA guidelines (Preferred Reporting Items Systematic Reviews Meta-Analyses). Results: into hepatocellular revealed dysregulation key (TFs) pathways. Transcription HNF4A, CEBPA, GATA4/6, PROX1, SOX9, HNF6/Onecut1, ONECUT2/HNF6β showed altered expression patterns, disrupting programming promoting populations Dysregulated Wnt/β-catenin, TGF-β, Hippo influenced fate decisions interactions with microenvironment, further contributing heterogeneity. NOTCH TBX3/18 highlighted complexity points critical role TFs transdifferentiation, providing interventions improve outcomes. Conclusion: The decline gene type-specific genes dysregulates programing hepatocytes involved homeostasis. multiple roles every gene/TF begin manifest themselves causing homeostasis, transdifferentiation. like along such as Wnt/β-catenin signaling, play crucial roles. disruption sets stage diverse phenotypes within microenvironment. vital developing strategies address

Language: Английский

Citations

0