MicroRNA-448 通过靶向 JAK1/STAT3 通路抑制胰腺导管腺癌的转移。
MicroRNA-448 suppresses metastasis of pancreatic ductal adenocarcinoma through targeting JAK1/STAT3 pathway.
机构信息
Department of Emergency, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
出版信息
Oncol Rep. 2017 Aug;38(2):1075-1082. doi: 10.3892/or.2017.5781. Epub 2017 Jul 3.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignant pancreatic tumor. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in tumorigenesis and progression of PDAC. In the present study, we demonstrated that miR-448 expression was downregulated in PDAC tissues and cell lines. Clinical association analysis indicated that low expression of miR-448 was associated with poor prognostic features and conferred a significant reduced survival of PDAC patients. Overexpression of miR-448 suppressed PDAC cell migration and invasion, while its loss showed the opposite effects on these cellular processes. In vivo experiments revealed that miR-488 restoration prohibited liver metastasis of PDAC in nude mice. Moreover, we found that Janus kinase 1 (JAK1) was a direct target gene of miR-448 in PDAC cells. We further demonstrated that the expression of JAK1 mRNA was upregulated in PDAC tissues. Notably, the expression of JAK1 mRNA was inversely correlated with the level of miR-448 in PDAC tissues. In addition, JAK1 knockdown showed similar effects of miR-448 on the metastasis of PDAC cells. JAK1/STAT3 pathway may be involved in the function of miR-448 in PDAC cells. Taken together, these findings suggest that miR-448 functions as a tumor suppressor in the development of PDAC through targeting the JAK1/STAT3 pathway.
胰腺导管腺癌 (PDAC) 是最常见的恶性胰腺肿瘤。微小 RNA (miRNA) 是一组小的、非蛋白编码的内源性 RNA,在 PDAC 的发生和发展中发挥着关键作用。在本研究中,我们证明了 miR-448 在 PDAC 组织和细胞系中表达下调。临床关联分析表明,miR-448 表达水平低与不良预后特征相关,并显著降低 PDAC 患者的生存时间。miR-448 的过表达抑制了 PDAC 细胞的迁移和侵袭,而其缺失则对这些细胞过程产生相反的影响。体内实验表明,miR-488 的恢复可抑制裸鼠 PDAC 的肝转移。此外,我们发现 Janus 激酶 1 (JAK1) 是 PDAC 细胞中 miR-448 的直接靶基因。我们进一步证明了 JAK1 mRNA 在 PDAC 组织中表达上调。值得注意的是,JAK1 mRNA 的表达与 PDAC 组织中 miR-448 的水平呈负相关。此外,JAK1 敲低显示出与 miR-448 相似的作用,可抑制 PDAC 细胞的转移。JAK1/STAT3 通路可能参与了 miR-448 在 PDAC 细胞中的功能。综上所述,这些发现表明,miR-448 通过靶向 JAK1/STAT3 通路在 PDAC 的发生发展中发挥肿瘤抑制作用。