Jiang Wenli, Gu Wen, Qiu Ronglin, He Songbing, Shen Chenglong, Wu Yaohao, Zhang Jie, Zhou Jiajia, Guo Yixing, Wan Daiwei, Li Zhixi, Deng Jiemin, Zeng Lexiang, Tang Jin, Zhou Jin, Zhi Qiaoming, Deng Xiaogeng
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China, 215006.
Anticancer Agents Med Chem. 2016;16(4):432-9. doi: 10.2174/1871520615666150507122142.
miR-101 is an outstanding tumor suppressor in various cancers, while its role in pancreatic cancer (PC) is still unknown. The aim of this study was to investigate the role of miR-101 in epithelial-to-mesenchymal transition (EMT) and its clinical relevance in PC. Our data showed that the miR-101 expression was significantly decreased in human PC tissues, compared to non-tumor counterparts (p<0.05), which was reversely correlated to clinical characteristics, including lymph node metastasis, more venous infiltration, higher expression of CA19-9 and TNM stage (p<0.05). Low miR-101 expression was also confirmed to be associated with a poorer overall survival rate in PC patients (p<0.05). We identified high-mobility group AT-hook 2 (HMGA2) gene as a putative target of miR-101 in PC by bioinformatics analysis, dual luciferase activity and western blot assay, and found that miR-101 could specifically target the HMGA2 3'-untranslated region (3'-UTR) (p<0.05). Knockdown of HMGA2 reversed EMT resembling that of miR-101 over-expression. An inverse correlation between miR-101 and HMGA2 was observed in patients with PC (p<0.05). Taken together, our findings speculated that miR-101 might act as an inhibiting factor in EMT process in PC and up-regulation of miR-101 might be considered as a potentially key molecular treatment strategy for PC patients.
miR-101在多种癌症中是一种显著的肿瘤抑制因子，但其在胰腺癌（PC）中的作用仍不清楚。本研究的目的是探讨miR-101在上皮-间质转化（EMT）中的作用及其在PC中的临床相关性。我们的数据显示，与非肿瘤对应组织相比，miR-101在人PC组织中的表达显著降低（p<0.05），这与包括淋巴结转移、更多的静脉浸润、CA19-9的高表达和TNM分期等临床特征呈负相关（p<0.05）。低miR-101表达也被证实与PC患者较差的总生存率相关（p<0.05）。通过生物信息学分析、双荧光素酶活性和蛋白质印迹分析，我们确定高迁移率族AT钩蛋白2（HMGA2）基因是PC中miR-101的一个假定靶点，并发现miR-101可以特异性靶向HMGA2的3'非翻译区（3'-UTR）（p<0.05）。敲低HMGA2可逆转EMT，类似于miR-101过表达的情况。在PC患者中观察到miR-101与HMGA2呈负相关（p<0.05）。综上所述，我们的研究结果推测，miR-101可能在PC的EMT过程中作为一种抑制因子，上调miR-101可能被认为是PC患者潜在的关键分子治疗策略。
