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Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder caused by the interaction of environmental factors and multiple genes. The genetic background of T2DM is complex and remains to be fully elucidated. MicroRNAs (miRNAs) are negative regulators of gene expression and several miRNAs are associated with the development of T2DM. However, the expression and biological function of miRNA-9-3p in lipid metabolism of patients with T2DM remain to be fully elucidated. The predominant aim of the present study was to examine the effect of miRNA-9-3p on lipid accumulation in HepG2 cells. To investigate this, an MTT assay was used to determine cell proliferation, and the effects of miRNA-9-3p on triglycerides (TG) and total cholesterol (TC) in the HepG2 cells were also examined. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to measure the expression levels of SIRT1 at the gene and protein levels, respectively. The date revealed that downregulation of miRNA-9-3p inhibited the proliferation of HepG2 cells, and significantly reduced the accumulation of lipids, and decreased TG and TC content. In addition, the present study demonstrated that inhibition of miRNA-9-3p increased the protein expression of sirtuin type 1 (SIRT1), but had no effects on the gene expression of SIRT1. Therefore, these findings demonstrated that the inhibition of miRNA-9-3p reduced the proliferation of HepG2 cells and lipid accumulation by upregulating the expression of SIRT1, indicating its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]