ArticleOncotarget2016
Restoring miR122 in human stem-like hepatocarcinoma cells, prompts tumor dormancy through Smad-independent TGF-β pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- The epigenetic regulator SETDB1 as a key component of cancer stem cells and drug resistance in primary liver cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Post-translational modification in hepatocellular carcinoma resistance: molecular mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- From Worms to Tumors: Conserved Strategies of Cellular Arrest and Survival Governing Dormancy.Cancer research · 2025Review
- Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Interleukin-17 programs liver progenitor cell transformation into cancer stem cells through miR-122 downregulation with increased risk of primary liver cancer initiation.International journal of biological sciences · 2022Article
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- Targeting transforming growth factor-β signaling for enhanced cancer chemotherapy.Theranostics · 2021Review
- MiR-17-5p and MKL-1 modulate stem cell characteristics of gastric cancer cells.International journal of biological sciences · 2021Article
- Tumor dormancy in bone.Cancer reports (Hoboken, N.J.) · 2020Review
- Dysregulated microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Potential as Biomarkers and Therapeutic Targets.Frontiers in oncology · 2020Review
- PRRX1 Regulates Cellular Phenotype Plasticity and Dormancy of Head and Neck Squamous Cell Carcinoma Through miR-642b-3p.Neoplasia (New York, N.Y.) · 2019Article
- miR-4666-3p and miR-329 Synergistically Suppress the Stemness of Colorectal Cancer Cells via Targeting TGF-β/Smad Pathway.Frontiers in oncology · 2019Article
- Antiapoptotic BCL-2 proteins determine sorafenib/regorafenib resistance and BH3-mimetic efficacy in hepatocellular carcinoma.Oncotarget · 2018Article
- MicroRNA regulation of liver cancer stem cells.American journal of cancer research · 2018Review
- The Diverse Mechanisms of miRNAs and lncRNAs in the Maintenance of Liver Cancer Stem Cells.BioMed research international · 2018Review
- Diagnostic and therapeutic potentials of microRNAs in cholangiopathies.Liver research (Beijing, China) · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
miR122 is the prevalent miRNA in adult healthy liver and it is responsible for liver stem cell differentiation towards hepatocyte lineage. Its expression is frequently lost in hepatocellular carcinoma (HCC). We studied the effects of restoring miR122 expression in a distinctive cell line derived from human HCC-BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability and undetectable miR122 expression. We generated a stable BCLC9 cell line that expresses miR122 (BCLC9-miR122). Restitution of miR122 in BCLC9 cells, decreases cell proliferation rate and reduces significantly tumor size in vivo. BCLC9-miR122 cells down-regulate expression of MYC, KLF4, FOXM1, AKT2 and AKT3 genes and up-regulate FOXO1 and FOXO3A gene expression. In addition, miR122 transfected cells decreased AKT2 kinase activation while decreased FOXO1 and FOXO3A protein inactivation. Reduction in tumor size in BCLC9-miR122 associated with an increase in p38MAPK protein expression and activation leading to a low phospho-ERK1/2 to phospho-p38 ratio. Treatment of miR122 positive cells with an inhibitor of TGFBR1 activation, abolished tumor dormancy program and recovered cell proliferation rate through a Smad-independent TGF-β response.HCC stem-like cells can be directed towards cell differentiation and tumor dormancy by restoring miR122 expression. We demonstrate, for the first time, that dormancy program is achieved through a Smad-independent TGF-β pathway. Restablishing miR122 expression is a promising therapeutic strategy that would work concurrently reducing tumor aggressiveness and decreasing disease recurrence.
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