ORIGINAL ARTICLE   

Minerva Biotechnology and Biomolecular Research 2021 March;33(1):12-8

DOI: 10.23736/S2724-542X.20.02631-2

Copyright © 2020 EDIZIONI MINERVA MEDICA

lingua: Inglese

miR-199a-3p inhibits proliferation of rat basilar artery smooth muscle cells by targeting mTOR

Aiqun LIU ¹, Minhui YANG ², Songfa CHEN ¹, Zhongxing PENG ¹, Shengpeng DIAO ¹, Weifeng WU ¹, Mingfan HONG ¹ ✉

¹ School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; ² Haikou Hospital, Xiangya School of Medicine, Central South University, Haikou, China

BACKGROUND: Abnormal proliferation of vascular smooth muscle cell (VSMC) is a key pathological feature of vascular remodeling. The cerebrovascular remodeling is a prominent feature of hypertension and considered as a major risk of ischemic stroke, but the associated molecular mechanisms remain to be fully elucidated.
METHODS: miR-199a-3p, mTOR, Ki-67 and PCNA expression were detected by qRT-PCR. miR-199a-3p/mTOR mimic or inhibitor was transfected into Basilar artery smooth muscle cells (BASMCs), the Western blot was facilitated to detect the level of mTOR. Proliferation of BASMCs was measured by MTS assay. The luciferase reporter experiment was conducted to reveal the direct interaction between miR-199a-3p and the 3′-UTR of mTOR.
RESULTS: We have found that miR-199a-3p was significantly downregulated in Ang II-induced BASMCs proliferation, Furthermore, we demonstrated that overexpression of miR-199a-3p inhibited mTOR expression, and potently suppressed Ang II-induced BASMCs proliferation. Then, we identified mTOR as downstream targets of miR-199a-3p in rat BASMCs, which playing a key role in Ang II-induced BASMCs proliferation.
CONCLUSIONS: These results indicate that miR-199a-3p is a novel modulator of BASMCs proliferation by targeting mTOR. These findings suggest that targeting miR-199a-3p or its downstream targets in rat BASMCs may represent an attractive approach for the treatment of cerebrovascular remodeling in hypertension-induced ischemic stroke.

KEY WORDS: Human mirn199 microRNA; Mouse mTOR protein; Angiotensin II; Basilar artery; Smooth muscle myocytes; Ischemia