Department of Neurosurgery, Hainan General Hospital, Haikou, P.R. China.
Biosci Biotechnol Biochem. 2020 May;84(5):911-918. doi: 10.1080/09168451.2020.1715780. Epub 2020 Jan 20.
Pituitary adenomas constitute one of the most common intracranial tumors. MicroRNAs play an important role in development and progression of pituitary adenomas. In this study, we showed that miR-219a-2-3p was significantly down-regulated in pituitary adenomas cells. Overexpression of miR-219a-2-3p suppressed the proliferation and promoted apoptosis of pituitary adenomas cells. After bioinformatics analysis, we found that MDM2 was one of the downstream targets of miR-219a-2-3p. Further researches showed that miR-219a-2-3p could reduce the protein level of MDM2 by binding to the 3'-UTR of MDM2 and promoted p53 expression. Then, we overexpressed both miR-219a-2-3p and MDM2 in the same group and found that it could counteract the effect of overexpressing miR-219a-2-3p alone on proliferation and apoptosis of pituitary adenoma cells. Taken together, these results suggested that miR-219a-2-3p regulated the proliferation and apoptosis by targeting MDM2/p53 in pituitary adenomas. Therefore, miR-219a-2-3p may serve as a novel marker and therapeutic target for pituitary adenomas.
垂体腺瘤是最常见的颅内肿瘤之一。 microRNAs 在垂体腺瘤的发生和发展中起重要作用。本研究表明,miR-219a-2-3p 在垂体腺瘤细胞中明显下调。过表达 miR-219a-2-3p 抑制了垂体腺瘤细胞的增殖并促进了凋亡。通过生物信息学分析,我们发现 MDM2 是 miR-219a-2-3p 的下游靶标之一。进一步的研究表明,miR-219a-2-3p 通过结合 MDM2 的 3'UTR 降低了 MDM2 的蛋白水平,并促进了 p53 的表达。然后,我们在同一组中同时过表达 miR-219a-2-3p 和 MDM2,发现它可以抵消单独过表达 miR-219a-2-3p 对垂体腺瘤细胞增殖和凋亡的影响。总之,这些结果表明,miR-219a-2-3p 通过靶向 MDM2/p53 调节垂体腺瘤的增殖和凋亡。因此,miR-219a-2-3p 可能作为垂体腺瘤的一种新的标志物和治疗靶点。