Zhao Shasha, Gao Xinyuan, Zang Shuzhi, Li Yunxia, Feng Xianjun, Yuan Xiaomei
Department of Respiratory Medicine, The First Hospital Affiliated to The Xinxiang Medical College, Xinxiang, Henan 453100, P.R. China.
Oncol Lett. 2017 Sep;14(3):3573-3579. doi: 10.3892/ol.2017.6603. Epub 2017 Jul 18.
Lung cancer is the leading cause of cancer-associated mortality worldwide. MicroRNAs (miRNAs/miRs) serve a role in the occurrence and development of lung cancer. The aim of the present study was to analyze the expression and function of the proliferation-associated miR-383-5p in lung adenocarcinoma (LAC). Samples of human LAC and matched adjacent normal lung tissues were surgically removed, and miR-383-5p expression and the pathological characteristics of lung adenocarcinoma were investigated. The present study revealed that miR-383-5p expression level was significantly decreased in LAC tissues and its expression levels were markedly associated with tumor size and differentiation. Overexpression of miR-383-5p in A549 and H1299 LAC cell lines inhibited cell proliferation by G cell cycle phase arrest and induction of apoptosis. Cancerous inhibitor of protein phosphatase 2A (CIP2A), a potential target gene of miR-383-5p, was inversely associated with miR-383-5p expression level in LAC tissues and cell lines. Furthermore, the results of the present study demonstrated that CIP2A was directly regulated by miR-383-5p and the restoration of CIP2A expression reversed the inhibitory effects of miR-383-5p on LAC cell proliferation. In conclusion, the results of the present study demonstrated that miR-383-5p was downregulated in LAC tissues. By targeting CIP2A, miR-383-5p exerts its anti-proliferative function in LAC, suggesting its use a potential novel potential prognostic biomarker and therapeutic target for LAC.
肺癌是全球癌症相关死亡的主要原因。微小RNA(miRNA/miR)在肺癌的发生和发展中发挥作用。本研究的目的是分析增殖相关的miR-383-5p在肺腺癌(LAC)中的表达及功能。手术切除人LAC样本及配对的相邻正常肺组织,研究miR-383-5p的表达及肺腺癌的病理特征。本研究显示,LAC组织中miR-383-5p表达水平显著降低,其表达水平与肿瘤大小和分化显著相关。在A549和H1299 LAC细胞系中过表达miR-383-5p可通过使细胞周期阻滞于G期并诱导凋亡来抑制细胞增殖。蛋白磷酸酶2A的癌性抑制剂(CIP2A)作为miR-383-5p的潜在靶基因,在LAC组织和细胞系中与miR-383-5p表达水平呈负相关。此外,本研究结果表明CIP2A受miR-383-5p直接调控,恢复CIP2A表达可逆转miR-383-5p对LAC细胞增殖的抑制作用。总之,本研究结果表明LAC组织中miR-383-5p表达下调。通过靶向CIP2A,miR-383-5p在LAC中发挥其抗增殖功能,提示其可作为LAC潜在的新型预后生物标志物和治疗靶点。