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

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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0facea68bb498dfe609fe28382110c08Test
http://link.springer.com/article/10.1038/s41419-018-0616-8Test

المؤلفون: Wangpeng Shi, Suning Liu, Dan Wang, Hang Zhou, Juanjuan Li, Long Zhang, Jie Shen

المصدر: Scientific Reports

مصطلحات موضوعية: 0301 basic medicine, animal structures, Genetic Vectors, Gene Expression, Locusta migratoria, Article, Conserved sequence, 03 medical and health sciences, parasitic diseases, Escherichia coli, Animals, Drosophila Proteins, Wings, Animal, Amino Acid Sequence, Cloning, Molecular, Transcription factor, Conserved Sequence, Phylogeny, Cell Proliferation, RNA, Double-Stranded, Homeodomain Proteins, Regulation of gene expression, Multidisciplinary, Wing, Sequence Homology, Amino Acid, biology, fungi, Gene Expression Regulation, Developmental, biology.organism_classification, Recombinant Proteins, Cell biology, MicroRNAs, Drosophila melanogaster, 030104 developmental biology, Sequence Alignment, Drosophila Protein, Function (biology), Locust, Signal Transduction, Transcription Factors

الوصف: Locusta has strong fly wings to ensure its long distance migration, but the molecular mechanism that regulates the Locusta wing development is poorly understood. To address the developmental mechanism of the Locusta flying wing, we cloned the Dpp target gene spalt (sal) and analyzed its function in wing growth in the Locusta. The Locusta wing size is apparently reduced with vein defects when sal is interfered by injection of dsRNA, indicating that sal is required for locust wing growth and vein formation. This function is conserved during the Drosophila wing development. To better understand sal’s function in wing growth, we then used Drosophila wing disc as a model for further study. We found that sal promotes cell proliferation in the whole wing disc via positive regulation of a microRNA bantam. Our results firstly unravel sal’s function in the Locusta wing growth and confirm a highly conserved function of sal in Locusta and Drosophila.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2250b283d0ce98180b1e761ad2a60f55Test