Xu Weihua, Jiang Kanqiu, Shen Mingjing, Chen Yongbing, Huang Hao-Yue
Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Oncol Rep. 2016 Jan;35(1):352-8. doi: 10.3892/or.2015.4349. Epub 2015 Oct 26.
Lung cancer has become the most common cancer worldwide, of which non-small cell lung cancer (NSCLC) accounts for over 80%. Previous studies have shown that the Jumonji domain containing 2A (JMJD2A) was aberrantly expressed in various tumors and involved in the regulation of tumor progression, but the role of JMJD2A on the tumorigenesis in NSCLC and the underlying mechanisms are still unclear. In the present study, we first identified the expression of JMJD2A in NSCLC tissues and cell lines through quantitative RT-PCR (qRT-PCR) and western blotting. Next, the effects of JMJD2A on the progression of NSCLC were analyzed. MTT assay was performed to measure the cell numbers and fluorescence-activated cell sorting (FACS) was adopted to evaluate cell apoptosis. Finally, the relationship between JMJD2A and miR-150 involved in NSCLC was studied. Our results suggested that JMJD2A was significantly overexpressed in NSCLC samples and cell lines. Kaplan-Meier analysis showed that high level of JMJD2A predicted a poor prognosis. Knockdown of JMJD2A inhibited tumor growth and promoted cell apoptosis in NSCLC cells. Additionally, miR-150 was upregulated in NSCLC tissues and positively related with JMJD2A expression. Significant downregulation of miR-150 was observed with JMJD2A knockdown. Furthermore, JMJD2A knockdown inhibited NSCLC cell proliferation while the silencing of miR-150 attenuated the inhibition effect on cell proliferation, suggesting that the effect of JMJD2A on NSCLC cell growth was dependent on miR-150. Thus, our findings identified that JMJD2A played an oncogenic role in NSCLC via regulating miR-150. JMJD2A could possibly serve as a prognostic factor and potential target for NSCLC therapy.
肺癌已成为全球最常见的癌症,其中非小细胞肺癌(NSCLC)占比超过80%。先前的研究表明,含Jumonji结构域2A(JMJD2A)在多种肿瘤中异常表达,并参与肿瘤进展的调控,但JMJD2A在NSCLC肿瘤发生中的作用及其潜在机制仍不清楚。在本研究中,我们首先通过定量逆转录聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法确定了JMJD2A在NSCLC组织和细胞系中的表达。接下来,分析了JMJD2A对NSCLC进展的影响。采用MTT法检测细胞数量,并采用荧光激活细胞分选(FACS)法评估细胞凋亡。最后,研究了JMJD2A与参与NSCLC的miR-150之间的关系。我们的结果表明,JMJD2A在NSCLC样本和细胞系中显著过表达。Kaplan-Meier分析显示,高水平的JMJD2A预示着预后不良。敲低JMJD2A可抑制NSCLC细胞的肿瘤生长并促进细胞凋亡。此外,miR-150在NSCLC组织中上调,且与JMJD2A表达呈正相关。敲低JMJD2A后,miR-150显著下调。此外,敲低JMJD2A可抑制NSCLC细胞增殖,而沉默miR-150可减弱对细胞增殖的抑制作用,这表明JMJD2A对NSCLC细胞生长的影响依赖于miR-150。因此,我们的研究结果表明,JMJD通过调节miR-150在NSCLC中发挥致癌作用。JMJD2A可能作为NSCLC治疗的预后因素和潜在靶点。