Department of Gastroenterology/Hepatology, ZhongNan Hospital of Wuhan University, Wuhan, China.
The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, China.
J Cell Biochem. 2018 Jun;119(6):4799-4807. doi: 10.1002/jcb.26676. Epub 2018 Mar 1.
miRNAs are small noncoding RNAs that act as critical epigenetic regulators in tumor carcinogenesis. In this study, our data showed that miR-137 was significantly downregulated in 58 pairs of human pancreatic cancer (PanCa) tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated with increased tumor size, higher TNM stage, and worse prognosis in pancreatic cancer. Functional studies demonstrated that overexpression of miR-137 dramatically suppressed cell proliferation and induced cell apoptosis in vitro. Meanwhile, upregulated miR-137 remarkably inhibited migration and invasion of pancreatic cancer cells. Further studies indicated that MRGBP was identified as the direct downstream target gene of miR-137. In addition, MRGBP expression is significantly downregulated in miR-137-transfected cells. Our previous study revealed that silencing of MRGBP suppressed the growth of PanCa cells in vitro and in vivo and also promoted apoptosis, and inhibited migration and invasion of PanCa cells, which are consistent with the effects of miR-137 overexpression. Taken together, our findings suggest that miR-137 may function as a novel tumor promoter through directly targeting MRGBP in PanCa.
miRNAs 是小的非编码 RNA,作为关键的表观遗传调控因子在肿瘤发生中起作用。在这项研究中,我们的数据显示 miR-137 在 58 对人胰腺导管腺癌 (PanCa) 组织和 PanCa 细胞系中显著下调。此外,失调的 miR-137 与胰腺癌中肿瘤体积增大、TNM 分期升高和预后不良相关。功能研究表明,miR-137 的过表达可显著抑制体外细胞增殖并诱导细胞凋亡。同时,上调的 miR-137 可显著抑制胰腺癌细胞的迁移和侵袭。进一步的研究表明,MRGBP 被鉴定为 miR-137 的直接下游靶基因。此外,在转染 miR-137 的细胞中,MRGBP 的表达明显下调。我们之前的研究表明,沉默 MRGBP 可抑制 PanCa 细胞在体外和体内的生长,并促进细胞凋亡,同时抑制 PanCa 细胞的迁移和侵袭,这与 miR-137 过表达的作用一致。总之,我们的研究结果表明,miR-137 可能通过直接靶向 PanCa 中的 MRGBP 发挥肿瘤促进作用。