MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma.
MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma.
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MicroRNA-432 通过靶向肺腺癌中的 E2F3 和 AXL 发挥抑癌基因的作用
DOI：
10.18632/oncotarget.7884
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发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Chen L;Kong G;Zhang C;Dong H;Yang C;Song G;Guo C;Wang L;Yu H
肺腺癌（LAD）的特征是细胞异常增殖和耐药。尽管在诊断和治疗方面取得了进展，但5年生存率仍然很低。microRNA（miRNA）因其具有节点调控特性，近年来对其病理机制的研究越来越多。本研究旨在探讨miR-432在LAD中的表达及其对肺癌细胞增殖和顺铂敏感性的影响。在此，我们报道了LAD组织中miR-432的下调与较高的临床分期（p = 0.03）和不良预后（p = 0.036）相关。此外，在我们的队列中，miR-432表达与高Ki 67标记指数（p = 0.016）负相关。在功能上，miR-432的过表达通过阻滞细胞周期来抑制细胞增殖，并使肿瘤细胞对顺铂敏感。从机制上讲，miR-432通过直接靶向E2 F3和AXL发挥作用，而E2 F3和AXL又介导miR-432对细胞增殖和顺铂敏感性的调节。重要的是，miR-432水平与人LAD组织中E2 F3和AXL的水平呈负相关。这些结果表明，miR-432作为肿瘤抑制性miRNA发挥作用，并可能代表LAD的预后参数和治疗靶点。
Abnormal proliferation and drug resistance are the hallmarks of lung adenocarcinoma (LAD). Dispite the advances in diagnosis and therapy, the 5-year survival remains low. Increasing studies regarding its pathological mechanism have been focused on microRNA (miRNA) due to its nodal regulatory properties. This study aims to characterize the expression of miR-432 in LAD and investigate its effects on the proliferation and sensitivity of lung cancer cells to cisplatin. Here, we report that downregulation of miR-432 in LAD tissues was correlated with a higher clinical stage (p = 0.03) and poor prognosis (p = 0.036). Additionally, miR-432 expression was negative correlated with high Ki67 labeling index (p = 0.016) in our cohorts. Functionally, over-expression of miR-432 inhibits cell proliferation through arresting cell cycle and sensitizes tumor cells to cisplatin. Mechanistically, miR-432 functions by directly targeting E2F3 and AXL, and they, in turn, mediate the regulation of miR-432 towards cell proliferation and cisplatin sensitivity. Importantly, miR-432 levels are negatively correlated with the levels of E2F3 and AXL in human LAD tissues. These results demonstrated that miR-432 functions as a tumor-suppressive miRNA and may represent a prognostic parameter and therapeutic target for LAD.