The Dept. of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, The City of Hangzhou, Zhejiang Province, PR China.
The Dept. of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Mol Cell Endocrinol. 2019 May 15;488:25-35. doi: 10.1016/j.mce.2019.02.020. Epub 2019 Mar 7.
Silencing of noncoding genes within the imprinted DLK1-MEG3 locus is exclusive to human nonfunctional pituitary adenomas (NFPAs), but the exact mechanism is still unclear. This study was designed to demonstrate the impact of CXCL12 on the expression of miRNAs within this locus and phenotypic alterations of NFPAs. Human NFPA samples were collected for screening differentially expressed miRNAs by CXCL12. Target mRNAs of the miRNAs were predicted and verified in vitro. Tumor phenotypic alterations were also tested. Another 51 NFPA samples were enrolled to examine the correlation and clinical features. The expression of miR-370 was decreased by CXCL12 treatment in NFPAs. miR-370-3p was predicted and verified to target HMGA2 as a tumor suppressor gene. Overexpression of HMGA2 inhibited its antitumor function. miR-370-3p was downregulated and HMGA2 was upregulated significantly in High grade NFPAs. In conclusion, the CXCL12/miR-370-3p/HMGA2 signaling pathway is involved in tumor growth and invasiveness of NFPAs.
印迹基因座 DLK1-MEG3 内非编码基因的沉默仅发生于人类无功能垂体腺瘤（NFPAs）中，但确切机制尚不清楚。本研究旨在证明 CXCL12 对该基因座内 miRNA 表达的影响以及 NFPAs 的表型改变。收集人 NFPA 样本，通过 CXCL12 筛选差异表达的 miRNA。预测并验证了 miRNA 的靶 mRNA。还检测了肿瘤表型的改变。另外 51 例 NFPA 样本被纳入研究，以检验其相关性和临床特征。CXCL12 处理可降低 NFPAs 中 miR-370 的表达。miR-370-3p 被预测并验证为 HMGA2 的肿瘤抑制基因靶点。HMGA2 的过表达抑制了其抗肿瘤功能。在高级别 NFPAs 中，miR-370-3p 下调，HMGA2 上调。综上所述，CXCL12/miR-370-3p/HMGA2 信号通路参与了 NFPAs 的肿瘤生长和侵袭。
