ABSTRACT

Pancreatic cancer (PC) is a leading cause of cancer mortality and is expected to continue increasing incidence. Abnormally expressed microRNAs have been demonstrated tightly correlated with the development and progression of PC. However, the molecular mechanisms remain largely unknown. In this study through combing both the TCGA database and our two verification PC cohorts, we found the consistent reduction of miR-3613-5p in PC tumors, which significantly correlated with reduced cumulative survival rate among PC patients. PC patients with higher lymph node metastasis rate show reduced miR-3613-5p expression. Through further mechanistic investigation, we demonstrate that miR-3613-5p down-regulated CDK6 in repressing the metastasis capacity of PC cells in vitro and in vivo. Elevated CDK6 were also found in PC samples, which also correlate with poor prognosis. Thus, our study found a novel tumor repressor miR-3613-5p in PC progression.

 抽象的

胰腺癌（PC）是癌症死亡的主要原因，预计发病率将继续增加。异常表达的 microRNA 已被证明与 PC 的发生和进展密切相关。然而，其分子机制仍然很大程度上未知。在这项研究中，通过结合 TCGA 数据库和我们的两个验证 PC 队列，我们​​发现 PC 肿瘤中 miR-3613-5p 持续减少，这与 PC 患者累积生存率的降低显着相关。淋巴结转移率较高的 PC 患者显示 miR-3613-5p 表达降低。通过进一步的机制研究，我们证明 miR-3613-5p 下调 CDK6 抑制 PC 细胞的体外和体内转移能力。 PC 样本中也发现 CDK6 升高，这也与不良预后相关。因此，我们的研究在 PC 进展中发现了一种新型肿瘤抑制因子 miR-3613-5p。