Abstract MicroRNAs (miRNAs) dysregulation is tightly related to diseases including tumor, neuro disease and cardiovascular disease. In this study, we investigated the potential biological effects of miR-34a and its target CXCR3 in phenotypic modulation of vascular smooth muscle cells (VSMCs) of intracranial aneurysms (IAs). MiR-34a was found to be down-regulated in IAs patients tested by Real-time PCR and decreased in GEO data. Meanwhile, our study also showed miR-34a inhibited matrix metalloproteinases (MMPs) and migration of VSMCs. Besides, CXCR3 is a direct target of miR-34a identified via luciferase assay. CXCR3 showed inhibitory effect on SM-MHC, SM22 while promoted MMPs expression, cell proliferation and migration in VSMCs. MiR-34a reversed the effect of CXCR3 in VSMCs. In addition, MMP-2 is a competitive endogenous RNA (ceRNA) of CXCR3 sharing common miR-34a target. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sponging endogenous miR-34a. In conclusion, miR-34a is down-regulated in IAs while CXCR3 is the direct target of miR-34a that regulates phenotypic modulation of VSMCs. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sharing common miR-34a targets.

中文翻译：

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miR-34a通过靶向CXCR3和MMP-2调节颅内动脉瘤中血管平滑肌细胞的表型调节

摘要MicroRNA（miRNA）失调与包括肿瘤，神经疾病和心血管疾病在内的疾病密切相关。在这项研究中，我们调查了miR-34a及其靶CXCR3在颅内动脉瘤（IAs）的血管平滑肌细胞（VSMC）的表型调节中的潜在生物学作用。发现MiR-34a在通过实时PCR测试的IAs患者中被下调，而GEO数据则下降。同时，我们的研究还显示miR-34a抑制基质金属蛋白酶（MMP）和VSMC迁移。此外，CXCR3是通过荧光素酶测定法鉴定的miR-34a的直接靶标。CXCR3显示出对SM-MHC，SM22的抑制作用，同时促进了VSMC中MMPs的表达，细胞增殖和迁移。MiR-34a逆转了VSMC中CXCR3的作用。此外，MMP-2是具有共同miR-34a靶标的CXCR3的竞争性内源RNA（ceRNA）。CXCR3通过竞争性内源性miR-34a的竞争性内源性RNA调节提高了MMP-2水平。总之，miR-34a在IAs中被下调，而CXCR3是miR-34a的直接靶标，它调节VSMC的表型调节。CXCR3通过共享常见的miR-34a靶标，通过竞争性内源RNA调节提高了MMP-2的水平。