Dynamic regulation of uncoupling protein 2 expression by microRNA-214 in hepatocellular carcinoma
| العنوان: | Dynamic regulation of uncoupling protein 2 expression by microRNA-214 in hepatocellular carcinoma |
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| المؤلفون: | Guangsheng Yu, Kesen Xu, Jianlu Wang, Jiahong Dong |
| المصدر: | Bioscience Reports |
| بيانات النشر: | Portland Press Ltd., 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Untranslated region, HepG2, Hepatoblastoma, Carcinoma, Hepatocellular, Cell, uncoupling proteins, Biophysics, S24, Context (language use), Biology, Biochemistry, S44, Cell Line, hepatocellular carcinoma (HCC), 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, microRNA, medicine, Humans, Uncoupling Protein 2, Antagomir, 3' Untranslated Regions, Molecular Biology, uncoupling protein 2 (UCP2), Cell Proliferation, Original Paper, Effector, Cell growth, Liver Neoplasms, Cell Biology, cell, medicine.disease, Original Papers, Molecular biology, digestive system diseases, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Liver, chemistry, S39, 030220 oncology & carcinogenesis, Cancer research |
| الوصف: | Our data indicate that in the context of HCC, miR-214 acts as a putative tumour suppressor by targeting UCP2 and defines a novel mechanism of regulation of UCP2. Gemcitabine (GEM), a commonly used chemotherapeutic agent in hepatocellular carcinoma (HCC) patients, uses oxidative stress induction as a common effector pathway. However, GEM alone or in combination with oxaliplatin hardly renders any survival benefits to HCC patients. We have recently shown that this is part due to the overexpression of the mitochondrial uncoupling protein 2 (UCP2) that in turn mediates resistance to GEM in HCC patients. However, not much is known about regulatory mechanisms underlying UCP2 overexpression in HCC. Differential protein expression in HCC cell lines did not show a concomitant change in UCP2 transcript level, indicating post-transcriptional or post-translational regulatory mechanism. In situ analysis revealed that UCP2 is a putative target of miR-214. miR-214 expression is significantly down-regulated in HCC patient samples as compared with normal adjacent tissues and in cell line, human hepatoblastoma cells (HuH6), with high UCP2 protein expression. We demonstrated using miR-214 mimic and antagomir that the miRNA targeted UCP2 expression by directly targeting the wild-type, but not a miR-214 seed mutant, 3’ UTR of UCP2. Overexpression of miR-214 significantly attenuated cell proliferation. Finally, analysis in 20 HCC patients revealed an inverse correlation in expression of UCP2 and miR-214 (Pearson's correlation coefficient, r=−0.9792). Cumulatively, our data indicate that in the context of HCC, miR-214 acts as a putative tumour suppressor by targeting UCP2 and defines a novel mechanism of regulation of UCP2. |
| تدمد: | 1573-4935 0144-8463 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85080f078051e05d299e199f17f0b7cd https://doi.org/10.1042/bsr20160062 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....85080f078051e05d299e199f17f0b7cd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15734935 01448463 |
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