Department of General Surgery, Shandong University School of Medicine, Jinan, China.
Eur Rev Med Pharmacol Sci. 2018 Feb;22(3):678-686. doi: 10.26355/eurrev_201802_14293.
Pancreatic cancer (PC) possesses a very poor prognosis, and its pathogenesis is not fully understood. Evidence has suggested that microRNAs play important roles in cancer development and progression, the present study was designed to study the function of miR-1271 in PC.
PC tissues and adjacent normal tissues were collected from 17 patients. MiR-1271 and PDK1 expression were quantified by quantitative reverse-transcriptional polymerase chain reaction (RT-PCR). AKT/MTOR signaling activity and PDK1 protein expression were determined by Western blot. Cell viability and apoptosis were assessed by MTT assay and enzyme-linked immunosorbent assay (ELISA). Luciferase assay was used to verify whether miR-1271 directly targets PDK1.
MiR-1271 was significantly down-regulated in PC tissues compared with that in the paired normal adjacent tissue, and its expression was up-regulated dose-dependently upon cisplatin treatment in PC cells. Overexpression of miR-1271 in these cells produced a pro-apoptotic effect, similar to what caused by cisplatin treatment. Moreover, overexpression of miR-1271 inhibited AKT/MTOR signaling, which was due to the targeting relationship between miR-1271 and PDK1. Finally, knockdown of PDK1 exerted a similar effect on apoptosis to that of miR-1271 overexpression.
MiR-1271 is a potent tumor suppressor in PC, its pro-apoptotic function was partially mediated by reduced AKT/MTOR signaling. Targeting miR-1271 may represent an effective strategy for PC treatment.
胰腺癌（PC）预后极差，其发病机制尚未完全阐明。有证据表明，microRNAs 在癌症的发生和发展中发挥着重要作用，本研究旨在研究 miR-1271 在 PC 中的作用。
收集了 17 名患者的 PC 组织和相邻正常组织。通过定量逆转录聚合酶链反应（RT-PCR）定量检测 miR-1271 和 PDK1 的表达。通过 Western blot 测定 AKT/MTOR 信号活性和 PDK1 蛋白表达。通过 MTT 检测和酶联免疫吸附测定（ELISA）评估细胞活力和细胞凋亡。通过荧光素酶报告实验验证 miR-1271 是否直接靶向 PDK1。
与配对的正常相邻组织相比，miR-1271 在 PC 组织中显著下调，并且在 PC 细胞中顺铂处理呈剂量依赖性地上调。这些细胞中 miR-1271 的过表达产生了促凋亡作用，类似于顺铂处理引起的作用。此外，miR-1271 的过表达抑制了 AKT/MTOR 信号，这是由于 miR-1271 和 PDK1 之间的靶向关系。最后，PDK1 的敲低对细胞凋亡的作用与 miR-1271 的过表达相似。
miR-1271 是 PC 中的一种有效的肿瘤抑制因子，其促凋亡功能部分通过降低 AKT/MTOR 信号介导。靶向 miR-1271 可能代表了治疗 PC 的一种有效策略。
