MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect
| العنوان: | MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect |
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| المؤلفون: | Xueliang Zuo, Yao Zhang, Zhiqiang Chen, Xuehao Wang, Long Zhang, Jindao Wu, Guoyong Han |
| المصدر: | Cell Death and Disease, Vol 9, Iss 5, Pp 1-14 (2018) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Carcinoma, Hepatocellular, Immunology, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, Glycolysis, Anaerobiosis, RNA, Neoplasm, lcsh:QH573-671, Cell growth, Chemistry, lcsh:Cytology, Liver Neoplasms, Cancer, Cell Biology, medicine.disease, Hypoxia-Inducible Factor 1, alpha Subunit, Warburg effect, G1 Phase Cell Cycle Checkpoints, Aerobiosis, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, Anaerobic glycolysis, 030220 oncology & carcinogenesis, Cancer cell, S Phase Cell Cycle Checkpoints, Cancer research, Signal transduction, Reprogramming |
| الوصف: | Glucose metabolic reprogramming from oxidative to aerobic glycolysis, referred as the Warburg effect, is a hallmark of tumor cells. Accumulating evidence suggests that a subset of microRNAs play pivotal roles in modulating such reprogramming of glucose metabolism in cancer cells. miR-3662 has been implicated previously in both pro-tumorigenic and anti-tumorigenic effects in several types of cancer. The expression level of miR-3662 is downregulated in acute myeloid leukemia, whereas increased miR-3662 expression is observed in lung adenocarcinoma. However, the roles and underlying mechanisms of miR-3662 in hepatocellular carcinoma (HCC) metabolic reprogramming remain unclear. Our present study revealed that miR-3662 was frequently downregulated in HCC tissues and cell lines. The low expression level of miR-3662 was associated with tumor size, tumor multiplicity, Edmondson grade, and tumor-node-metastasis stage. Gain-of-function and loss-of-function assays showed that miR-3662 dampened glycolysis by reducing lactate production, glucose consumption, cellular glucose-6-phosphate level, ATP generation, and extracellular acidification rate, and increasing oxygen consumption rate in HCC cells after treatment with the hypoxia mimetic CoCl2. Moreover, miR-3662 suppressed cell growth in vitro and in vivo, and induced G1/S cell cycle arrest. miR-3662 inhibited the activation of ERK and JNK signaling pathways in HCC. By combined computational and experimental approaches, hypoxia-inducible factor-1α (HIF-1α) was determined as a direct target of miR-3662. After treatment with the hypoxia mimetic CoCl2, miR-3662 regulated the Warburg effect and HCC progression via decreasing HIF-1α expression. Our findings uncover a mechanistic role for miR-3662/HIF-1α axis in HCC metabolic reprogramming, providing a potential therapeutic strategy in liver cancer. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0facea68bb498dfe609fe28382110c08Test http://link.springer.com/article/10.1038/s41419-018-0616-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0facea68bb498dfe609fe28382110c08 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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