ArticlePloS one2012
ER stress negatively modulates the expression of the miR-199a/214 cluster to regulates tumor survival and progression in human hepatocellular cancer.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Pooled it
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- MiR-34c-5p Inhibition Affects Bax/Bcl2 Expression and Reverses Bortezomib Resistance in Multiple Myeloma Cells.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2024Article
- Article
- Delivery of miR-214 via extracellular vesicles downregulatesExtracellular vesicles and circulating nucleic acids · 2024Article
- NF-κB downstream miR-1262 disturbs colon cancer cell malignant behaviors by targeting FGFR1.Acta biochimica et biophysica Sinica · 2023Article
- Pro-Apoptotic Activity of the Marine SpongeMarine drugs · 2022Article
- miRNAs as Biomarkers and Possible Therapeutic Strategies in Synovial Sarcoma.Frontiers in pharmacology · 2022Review
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- MicroRNA-214 in Health and Disease.Cells · 2021Review
- CircADARB1 serves as a new biomarker in natural killer T-cell lymphoma and a potential regulator of p-Stat3.Cancer cell international · 2021Article
- Let-7a-5p, miR-100-5p, miR-101-3p, and miR-199a-3p Hyperexpression as Potential Predictive Biomarkers in Early Breast Cancer Patients.Journal of personalized medicine · 2021Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Human Corneal Endothelial Cells from Endoplasmic Reticulum Stress-Mediated Apoptosis.International journal of molecular sciences · 2021Article
- Endoplasmic Reticulum Stress and miRNA Impairment in Aging and Age-Related Diseases.Frontiers in aging · 2021Review
- The Role of miRNAs during Endoplasmic Reticulum Stress Induced Apoptosis in Digestive Cancer.Journal of Cancer · 2021Review
- Involvement of miR-190b in Xbp1 mRNA Splicing upon Tocotrienol Treatment.Molecules (Basel, Switzerland) · 2020Article
- Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer.Journal of hematology & oncology · 2020Review
- Chaperone Sigma1R and Antidepressant Effect.International journal of molecular sciences · 2020Review
- MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy.Cardiovascular diabetology · 2020Review
- The Effect of miR-98 and miR-214 on Apoptotic and Angiogenic Pathways in Hepatocellular Carcinoma HepG2 Cells.Indian journal of clinical biochemistry : IJCB · 2020Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent studies have emphasized causative links between microRNAs (miRNAs) deregulation and tumor development. In hepatocellular carcinoma (HCC), more and more miRNAs were identified as diagnostic and prognostic cancer biomarkers, as well as additional therapeutic tools. This study aimed to investigate the functional significance and regulatory mechanism of the miR-199a2/214 cluster in HCC progression. METHODS AND
findingsIn this study, we showed that miR-214, as well as miR-199a-3p and miR-199a-5p levels were significantly reduced in the majority of examined 23 HCC tissues and HepG2 and SMMC-7721 cell lines, compared with their nontumor counterparts. To further explore the role of miR-214 in hepatocarcinogenesis, we disclosed that the ER stress-induced pro-survival factor XBP-1 is a target of miR-214 by using western blot assay and luciferase reporter assay. Re-expression of miR-214 in HCC cell lines (HepG2 and SMMC-7721) inhibited proliferation and induced apoptosis. Furthermore, ectopic expression of miR-214 dramatically suppressed the ability of HCC cells to form colonies in vitro and to develop tumors in a subcutaneous xenotransplantation model of the BALB/c athymic nude mice. Moreover, reintroduction of XBP-1s attenuated miR-214-mediated suppression of HCC cells proliferation, colony and tumor formation. To further understand the mechanism of the miR-199a/214 cluster down-expression in HCC, we found that thapsigargin (TG) and tunicamycin (TM) or hypoxia-induced unfolded protein response (UPR) suppresses the expression of the miR-199a/214 cluster in HCC cells. By promoter analysis of the miR-199a2/214 gene, we conjectured NFκB as a potential negative regulator. We further found that UPR and LPS-induced NFκB activation suppressed miR-199a2/214 transcription, and this suppression was reversed by NFκB inhibition in HCC cells.
conclusionsOur study suggest that modulation of miR-214 levels may provide a new therapeutic approach for cancer treatment and revealed that UPR may offer a new explanation for why the miR-199a/214 cluster were down-regulated in the progression in HCC.
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