ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2021
miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 14 citations in OpenAlex.
- miR-140-5p Inhibition alleviates LPS-induced cholangitis in rats and is associated with modulation of the NF-κB signaling pathway.Scientific reports · 2026Article
- PPP1CC Suppresses Preadipocyte Differentiation in Chickens at Least Partly by Regulating NRF1 Expression.Genes · 2026Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Single-cell and transcriptomic analyses reveal the influence of diabetes on ovarian cancer.BMC genomics · 2024Article
- Article
- MicroRNA-140-5p inhibitor attenuates memory impairment induced by amyloid-ß oligomer in vivo possibly through Pin1 regulation.CNS neuroscience & therapeutics · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMuch attention has been paid to the regulatory role of microRNA (miRNA) in insulin resistance. Nevertheless, how miR-140-5p regulates insulin resistance remains unclear. In this research, we aim to investigate the roles of miR-140-5p in insulin resistance.
methodsqRT-PCR is used to analyze the expression level of miR-140-5p in insulin-resistant HepG2 cells. Glucose consumption and glucose uptake are detected to study the effect of miR-140-5p knockdown in insulin-resistant HepG2 cells and miR-140-5p overexpression in HepG2 cells. Bioinformatic analysis, luciferase reporter assay and confirmatory experiments are applied to identify the target gene bound with miR-140-5p and study the effect of miR-140-5p on the downstream substrates of target genes. Rescue experiments have verified the roles of miR-140-5p and target gene in glucose metabolism.
resultsThe expression level of miR-140-5p was upregulated in insulin-resistant HepG2 cells and was significantly correlated with cellular glucose metabolism. Functionally, miR-140-5p overexpression induced impairment of glucose consumption and glucose uptake. Besides, bioinformatics analysis indicated that glycogen synthetase (GYS1) and protein phosphatase 1 catalytic subunit gamma (PPP1CC) were the target genes of miR-140-5p. Western blotting and qRT-PCR results revealed a negative correlation between GYS1, PPP1CC and miR-140-5p. The glycogen detection results showed that miR140-5p inhibited the production of the downstream substrates of the target gene. Rescue experiments showed that inhibition of GYS1 or PPP1CC partially enhanced the insulin-resistant effects of miR-140-5p knockdown in insulin-resistant HepG2 cells.
conclusionmiR-140-5p overexpression augments the development of insulin resistance and miR-140-5p may be served as a therapeutic target of metabolic diseases.
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