Neoplasma Vol.69, No.4, p.820–831, 2022
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| Title: The oncogenic miR-27a/BTG2 axis promotes obesity-associated hepatocellular carcinoma by mediating mitochondrial dysfunction |
| Author: Qi Su, Zi-Xin Xu, Min-Li Xiong, Hui-Yi Li, Ming-Yi Xu, Sheng-Zheng Luo |
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Abstract: Obesity is closely related to the initiation and development of hepatocellular carcinoma (HCC). The regulatory mechanism of obesity-associated HCC remains unclear. HepG2 cells treated with palmitic acid (PA) and diethylnitrosamine (DEN)-induced HCC mice fed a high-fat diet (HFD) were established. The expression of miR-27a and B-cell translocation gene 2 (BTG2) mRNA and protein were detected via qPCR and western blotting. Prediction software and luciferase assays were employed to verify the miR-27a/BTG2 axis. The biological effects of HepG2 cells were evaluated with ORO staining, MTT assays, Transwell assays, Mito-Timer, and Mito-SOX staining. Significantly upregulated miR-27a and downregulated BTG2 mRNA and protein were observed in HepG2 cells and liver tissues of HCC mice. Overexpressing miR27a (mi-miR27a) markedly promoted cellular lipid accumulation, proliferation, and invasion, accompanied by aggravated mitochondrial dysfunction (increased fading and ROS products of mitochondria) in HepG2 cells. Additionally, these effects were further reinforced in HepG2 cells treated with mi-miR27a and PA. BTG2 was identified as a direct target and was negatively regulated by miR-27a. Similarly, BTG2 knockdown (sh-BTG2) had effects identical to those of mi-miR27a on HepG2 cells. Additionally, PA evidently enhanced these effects of sh-BTG2 in HepG2 cells. Moreover, BTG2 overexpression effectively reversed the effects of miR-27a, including lipotropic and oncogenic effects, and simultaneously promoted mitochondrial imbalance in HepG2 cells. Thus, obesity-associated miR-27a acts as an oncogene to promote lipid accumulation, proliferation, and invasion by negatively regulating BTG2-mediated mitochondrial dysfunction in HCC.
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| Keywords: hepatocellular carcinoma (HCC); microRNA-27a (miR27a); B-cell translocation gene 2 (BTG2); obesity; mitochondria |
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Published online: 09-May-2022
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| Year: 2022, Volume: 69, Issue: 4 |
Page From: 820, Page To: 831 |
doi:10.4149/neo_2022_211227N1837
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