Implications of Possible HBV-Driven Regulation of Gene Expression in Stem Cell-like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line.
Ayse Banu DemirDomenico BenvenutoBilge KaracicekYasemin EracSilvia SpotoSilvia AngelettiMassimo CiccozziMetiner TosunPublished in: Journal of personalized medicine (2022)
Elevated levels of STIM1, an endoplasmic reticulum Ca 2+ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV origins of specific microRNAs we identified in a stem cell-like subpopulation of Huh-7 hepatocellular carcinoma (HCC) cell lines with enhanced STIM1 and/or Orai1 expression that mimicked poor cancer prognosis. Computational strategies including phylogenetic analyses were performed on miRNome data we obtained from an EpCAM- and CD133-expressing Huh-7 HCC stem cell-like subpopulation with enhanced STIM1 and/or Orai1 expression originally cultured in the present work. Results revealed two putative regions in the HBV genome based on the apparent clustering pattern of stem loop sequences of microRNAs, including miR3653. Reciprocal analysis of these regions identified critical human genes, of which their transcripts are among the predicted targets of miR3653, which was increased significantly by STIM1 or Orai1 enhancement. Briefly, this study provides phylogenetic evidence for a possible HBV-driven epigenetic remodeling that alters the expression pattern of Ca 2+ homeostasis-associated genes in STIM1 - or Orai1 overexpressing liver cancer stem-like cells for a possible mutual survival outcome. A novel region on HBV-X protein may affect liver carcinogenesis in a genotype-dependent manner. Therefore, detection of the viral genotype would have a clinical impact on prognosis of HBV-induced liver cancers.
Keyphrases
- hepatitis b virus
- stem cells
- liver failure
- gene expression
- poor prognosis
- long non coding rna
- binding protein
- cell proliferation
- papillary thyroid
- endothelial cells
- endoplasmic reticulum
- genome wide
- dna methylation
- single cell
- magnetic resonance imaging
- squamous cell
- computed tomography
- magnetic resonance
- amino acid
- high glucose
- young adults
- protein kinase
- oxidative stress
- transcription factor
- electronic health record
- bioinformatics analysis
- protein protein
- childhood cancer
- data analysis
- contrast enhanced
- sensitive detection
- cell therapy