miR-96-5p Regulates Proliferation, Migration, and Apoptosis of Vascular Smooth Muscle Cell Induced by Angiotensin II via Targeting NFAT5.

Background: Aberrant proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) are major pathological phenomenon in hypertension. MicroRNAs (miRNAs/miRs) serve crucial roles in the progression of hypertension. We aimed to determine the role of miR-96-5p in the proliferation, migration, and apoptosis of VSMCs and its underlying mechanisms.

Methods: Angiotensin II (Ang II) was employed to treat VSMCs, and the expression of miR-96-5p was detected by RT-qPCR. Then, miR-96-5p mimic was transfected into VSMCs. Cell Counting Kit-8 assay, flow cytometry, transwell assay, and wound healing assay were applied to measure proliferation, cell cycle, and migration of VSMCs. The expression of proteins associated with proliferation, migration, and apoptosis was assessed. A luciferase reporter assay was applied to confirm the target binding between miR-96-5p and nuclear factors of activated T-cells 5 (NFAT5). Subsequently, siRNA was used to silence NFAT5, and cell proliferation, migration, and apoptosis were assessed.

Results: The results revealed that the expression of miR-96-5p was downregulated in Ang II-induced VSMCs. MiR-96-5p overexpression inhibited cell proliferation and migration but promoted cell apoptosis, enhanced the percentages of cells in the G1 and G2 phases, and reduced those in the S phase, accompanied by changes in the expression associated proteins. NFAT5 was confirmed as a direct target of miR-96-5p. NFAT5 silencing had the same results with miR-96-5p overexpression on VSMC proliferation, migration, and apoptosis, whereas miR-96-5p inhibitor reversed these effects.

Conclusions: Our findings concluded that miR-96-5p could regulate proliferation, migration, and apoptosis of VSMCs induced by Ang II via targeting NFAT5.