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Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (m6A) methylation modification mediates the VSMC proliferation. This study aimed to reveal the m6A methylation modification regulatory mechanism. In this study, m6A demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated m6A methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and m6A-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to m6A methylation modified mRNA. In vivo studies confirmed that the elevated m6A modification level of SM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, m6A methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM. [ABSTRACT FROM AUTHOR]

Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (m 6 A) methylation modification mediates the VSMC proliferation. This study aimed to reveal the m 6 A methylation modification regulatory mechanism. In this study, m 6 A demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated m 6 A methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and m 6 A-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to m 6 A methylation modified mRNA. In vivo studies confirmed that the elevated m 6 A modification level of SM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, m 6 A methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Understanding mechanisms of cancer metastasis is crucial for reduction of cancer mortality. Acyl-CoA medium-chain synthetase 3 (ACSM3) is an acyl-CoA synthetase which takes part in the first step of fatty acid metabolism. However, the expression, clinical significance and biological function of ACSM3 remain unknown in hepatocellular carcinoma (HCC). In this study, the expression and prognostic relevance of ACSM3 were investigated by tissue microarray and HCC clinical samples. Migration and invasion assays were carried out for functional analysis in vitro and a xenograft model was used to analyze the effects of ACSM3 on cancer metastasis in vivo. Furthermore, human phospho-kinase array assays were performed to explore molecular mechanisms of ACSM3 in HCC. The results showed ACSM3 was downregulated in HCC tissues. HCC patients with low expression of ACSM3 exhibited poor prognosis. Overexpression of ACSM3 attenuated migration and invasion of HCC cells in vitro and in vivo and downregulated the phosphorylation of WNK1 and AKT. Our findings indicate ACSM3 is a novel prognostic marker and a potential therapeutic target for HCC.