MiR-154-3p Promotes Gastric Cancer Cell Proliferation And Migration Through SIRT1/NF-?B Signaling Pathway

Objective:To explore the role of miR-154-3p in the regulation of SIRT1 in gastric cancer and the mechanism affecting the development of gastric cancer Methods: The expression level of miR-154-3p and SIRT1 in gastric cancer cell lines were tested by qRT-PCR and Western Blot,which were also uesed to test the regulation of miR-154-3p on SIRT1 mRNA and protein expression.Whether the miR154-3p combined the 3'-UTR of SIRT1 was validated by Dual-Luciferase Reporter Assay.The impact of miR-154-3p on gastric cancer cell proliferation was evaluated by CCK-8 and clone formation assays.And the migration was evaluated by wound healing and transwellassays.The different expression of miR-154-3p in gastric cancer and paracancerous tissues of 31 patients were detected by qRT-PCR and the expression of SIRT1 in 18 patients weretested by immunohistochemical staining.The phosphorylation levels of NF-?B p65,ERK1/2 and AKT,downstream of SIRT1,were detected by Western Blot after transfecting miR-154-3p mimics or inhibitor in gastric cancer cells.Results:The expression level of miR-154-3p and SIRT1 were opposite in five kinds of gastric cancer cell lines.The miR-154-3p could down-regulate the protein expression of SIRT1 but not the mRNA expression.Dual-luciferase reporter assay showed that miR-154-3p could bind to SIRT1 3'-UTR directly.The overexpression of miR-154-3p significantly promoted the gastric cancer cell proliferation,colony formation and migration,while the inhibitor suppressed.Compared with the paracancerous tissues,the expression of miR154-3p significantly increased in gastric cancer tissues.The protein expression of SIRT1 decreased in carcinoma tissues.Overexpression of miR-154-3p significantly improved the phosphorylation level of NF-?B p65 but not the phosphorylation level of ERK1/2 and AKT.Conclusion:The miR-154-3p promotes the gastric cancer cell proliferation and migration through inhibits the translation of SIRT1 by targeting SIRT1 3'-UTR and promotsthe activaty of NF-?B p65 signal pathway.