MicroRNA-29b targeting of cell division cycle 7-related protein kinase (CDC7) regulated vascular smooth muscle cell (VSMC) proliferation and migration

MicroRNA-29b 靶向细胞分裂周期 7 相关蛋白激酶 (CDC7) 调节血管平滑肌细胞 (VSMC) 增殖和迁移

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作者:Qunhua Ma, Jing Zhang, Ming Zhang, Huan Lan, Qian Yang, Chengping Li, Li Zeng

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).

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.

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.

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