Shao Mingchen, Geng Yiwei, Lu Peng, Xi Ying, Wei Sidong, Wang Liuxing, Fan Qingxia, Ma Wang
Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou, China.
Gastrointestinal Surgery Department, People's Hospital of Zhengzhou, Zhengzhou, China.
Biochem Biophys Res Commun. 2015 Sep 4;464(4):1309-1313. doi: 10.1016/j.bbrc.2015.07.128. Epub 2015 Jul 29.
MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention.
微小RNA(miRNA)通过在转录后水平负向调控基因表达,在多种癌症的发病机制中发挥重要作用。然而,微小RNA在间变性甲状腺癌(ATC)中的作用仍不明确。在此,我们发现miR-4295通过负向调控其靶基因CDKN1A促进ATC细胞增殖。在ATC细胞系中,CCK-8增殖试验表明miR-4295促进细胞增殖,而miR-4295抑制剂显著抑制细胞增殖。Transwell试验表明,miR-4295模拟物显著促进ATC细胞的迁移和侵袭,而miR-4295抑制剂显著降低细胞迁移和侵袭。荧光素酶试验证实miR-4295直接与CDKN1A的3'非翻译区结合,蛋白质印迹法表明miR-4295在蛋白质水平上抑制CDKN1A的表达。本研究表明,miR-4295负向调控CDKN1A并促进ATC细胞系的增殖和侵袭。因此,miR-4295可能是ATC干预的潜在治疗靶点。