We previously identified genomic variants that are quantitative trait loci for circulating miR-1908-5p and then showed this microRNA to causally associate with plasma levels of LDL-C, fasting blood glucose and HbA1c. The link to LDL-C was subsequently validated and clarified by the identification of a miR1908-5p-TGFB-LDLR regulatory axis. Here, we continue our investigations on miR1908-5p function by leveraging human primary hepatocytes and HuH-7 hepatoma models. Expression of miR1908-5p was shown to be sensitive to glucose and agents affecting glucose metabolism. Transcriptome-wide changes in primary hepatocytes and HuH-7 cells treated with a miR1908-5p mimic were investigated by enrichment approaches to identify targeted transcripts and cognate pathways. Significant pathways included autophagy and increased mitochondrial function. Reduced activation and/or levels of several key energy and metabolic regulators (AKT, mTOR, ME1, G6PD, AMPK and LKB) were subsequently confirmed in mimic treated HuH-7 cells. These effects were associated with reduced NADPH to NADP+ ratio in HuH-7 cells. LKB1 was validated as a direct target of miR1908-5p, the reintroduction of which was however insufficient to compensate for the impact of the miR1908-5p mimic on AMPK and ACC1. These findings implicate miR1908-5p in metabolic and energy regulation in hepatocyte models via multiple, independent, pathways.
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http://dx.doi.org/10.1038/s41598-021-03156-4 | DOI Listing |
Front Cell Infect Microbiol
January 2025
College of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
Introduction: Coronavirus disease 2019 (COVID-19) is characterized by fever, fatigue, dry cough, dyspnea, mild pneumonia and acute lung injury (ALI), which can lead to acute respiratory distress syndrome (ARDS), and SARS-CoV-2 can accelerate tumor progression. However, the molecular mechanism for the increased mortality in cancer patients infected with COVID-19 is unclear.
Methods: Colony formation and wound healing assays were performed on Huh-7 cells cocultured with syncytia.
Eur J Med Chem
January 2025
College of Chemistry, Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address:
Incorporating fluorine-containing groups into the chemical skeleton is expected to enhance bioactivity and bioavailability. Directly introducing fluorine groups into the parthenolide skeleton remains challenging and limited. In this research, a series of novel fluorine-containing parthenolide derivatives were synthesized through late-stage diversification strategy.
View Article and Find Full Text PDFNarra J
December 2024
Department of Histology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.
The most common type of liver cancer is hepatocellular carcinoma (HCC), accounting for 75-85% of cases. Despite its associated side effects, sorafenib remains the standard treatment for HCC. Given the critical need to improve therapeutic efficacy while minimizing adverse effects, alternative drugs must be thoroughly investigated.
View Article and Find Full Text PDFBMC Cancer
January 2025
Jiangxi Provincial Key Laboratory of Child Development and Genetics, Jiangxi Provincial Children's Hospital, No. 122 of YangMing Road, DongHu District, NanChang, 330006, China.
Background: Hepatocellular carcinoma (HCC) is a prevalent primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, the 5-year survival rate for individuals undergoing curative resection remains between 10% and 15%. Consequently, identifying molecular targets that specifically inhibit the proliferation and metastasis of HCC cells is critical for improving treatment outcomes.
View Article and Find Full Text PDFJ Gastroenterol
January 2025
Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, China.
Background: We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC).
Methods: The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression.
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