MicroRNA-145 inhibits the activation of the mTOR signaling pathway to suppress the proliferation and invasion of invasive pituitary adenoma cells by targeting AKT3 in vivo and in vitro

Abstract

Kai Zhou, Yan-Dong Fan, Peng-Fei Wu, Serick Duysenbi, Zhao-Hai Feng, Guo-Jia Du, Ting-Rong Zhang Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China Purpose: This study was designed to explore how miR-145 regulates the mTOR signaling pathway in invasive pituitary adenoma (IPA) by targeting AKT3.Methods: A total of 71 cases of IPA tissues and 66 cases of non-IPA tissues were obtained in this study. In vitro, the IPA cells were assigned into blank control, empty plasmid, miR-145 mimic, miR-145 inhibitor, miR-145 mimic + rapamycin, miR-145 inhibitor + rapamycin and rapamycin groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect the protein expressions of PI3K, AKT3, mTOR mRNA and the mRNA expression of miR-145 both in vivo and in vitro. Additionally, the S6K and RPS6 mRNA and protein expressions as well as the relative phosphorylation levels were determined in vitro. MTT assay, flow cytometry and transwell assay were used to testify the cell proliferation, apoptosis and invasion ability, respectively.Results: The IPA tissues exhibited significantly lower expression of miR-145 but higher PI3K, AKT3 and mTOR mRNA and protein expressions when compared with the non-IPA tissues. Compared with the blank control and empty plasmid groups, the miR-145 mimic group showed significantly decreased PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as phosphorylation levels; besides, the IPA cell proliferation, migration and invasion ability were strongly inhibited, accompanied with the increased number of apoptotic cells. In the miR-145 inhibitor group, the PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as the phosphorylation levels were significantly increased; cell proliferation, migration and invasion ability were remarkably elevated, accompanied with reduced apoptotic cell number.Conclusion: The study demonstrates that miR-145 inhibits the mTOR signaling pathway to suppress the IPA cell proliferation and invasion and promotes its apoptosis by targeting AKT3. Keywords: invasive pituitary adenoma, microRNA-145, mTOR signaling pathway, proliferation, invasion, AKT3

Keywords

• Invasive pituitary adenoma
• MicroRNA-145
• mTOR signaling pathway
• Proliferation
• Invasion
• AKT3.