CircSFMBT2 facilitates vascular smooth muscle cell proliferation by targeting miR-331-3p/HDAC5

Objective: To investigate the functional role of circSFMBT2 in vascular smooth muscle cell (VSMC) proliferation and migration and the underlying molecular mechanism.

Methods: The circSFMBT2 levels in neointimal tissue and platelet derived growth factor-BB (PDGF-BB)-treated VSMCs were detected by qRT-PCR. The role of circSFMBT2 in VSMC proliferation, migration and cell cycle distribution was assessed by MTT assay, transwell assay, wound healing assay and flow cytometry. The protein expression of contractile markers was evaluated by western blot. In vitro luciferase reporter assay, RNA pull-down assay, ChIP and coimmunoprecipitation (CoIP) were performed to explore the effects of circSFMBT2 on the downstream signaling pathway.

Results: We found that circSFMBT2 was markedly increased in neointimal tissue relative to normal tissue and PDGF-BB-treated VSMCs relative to control VSMCs. The knockdown of circSFMBT2 by siRNA significantly inhibited the proliferation and migration of VSMCs. Interestingly, circSFMBT2 knockdown enhanced the expression of contractile marker proteins including SM22α, SM myosin heavy chain (SMMHC) and calponin. Further data demonstrated that circSFMBT2 interacted with miR-331-3p as a competing endogenous RNA and up-regulated the expression of histone deacetylase 5 (HDAC5), thereby regulating the level of angiogenic factor with G patch and FHA domains (Aggf1).

Conclusion: These results revealed that circSFMBT2 plays a vital role in VSMC proliferation and migration through the miR-331/HDAC5/Aggf1 axis, and suggest a novel target for treating proliferative vascular diseases.