MicroRNA-29b targeting of cell division cycle 7-related protein kinase (CDC7) regulated vascular smooth muscle cell (VSMC) proliferation and migration
Qunhua Ma, Jing Zhang, Ming Zhang, Huan Lan, Qian Yang, Chengping Li, Li Zeng
Abstract
BACKGROUND: Proliferation and migration of vascular smooth muscle cells (VSMCs) are vital processes in vascular remodeling and pathology. This study aimed to explore the expression of miR-29b and cell division cycle 7-related protein kinase (CDC7) in patients with cerebral aneurysm (CA) and their effects on the proliferation and mobility of human umbilical artery smooth muscle cells (HUASMCs). METHODS: RNA levels of miR-29b and CDC7 were evaluated in the CA tissues and adjacent normal cerebral arteries from 18 patients undergoing surgery for CA rupture. The targeting of CDC7 by miR-29b was verified with luciferase reporter assay. Both CDC7 and miR-29b overexpression and silencing vectors were introduced to validate their effects on the proliferation and mobility of HUASMCs. RESULTS: The mRNA level of miR-29b was down-regulated (P<0.05), while the mRNA level of CDC7 was markedly elevated in CA patients (P<0.05). A Luciferase reporter assay showed CDC7 is a target gene of miR-29b, and miR-29b mimic down-regulated the mRNA and protein levels of CDC7 (P<0.05). Furthermore, miR-29b mimic inhibited, while miR-29b inhibitor or CDC7 over-expression promoted the proliferation and mobility of HUASMCs (P<0.05). CONCLUSIONS: miR-29-3p inhibits cell proliferation and mobility via directly targeting CDC7, which could be a potential therapeutic target for vascular dysfunction related diseases, including atherosclerosis and CA.