Li Xiumei, Yu Zhuang, Li Yong, Liu Shihai, Gao Caihong, Hou Xin, Yao Ruyong, Cui Lianhua
Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Department of Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Int J Oncol. 2015 Feb;46(2):798-808. doi: 10.3892/ijo.2014.2786. Epub 2014 Dec 1.
The aim of the present study was to investigate the role of miR-124 in lung cancer and identify the potential predictive value of miR-124 in postoperative non-small cell lung cancer (NSCLC) patients. We detected miR-124 expression in A549, NCL-H460 and normal lung epithelial BEAS-2E cells and showed a significantly lower expression level of miR-124 in NSCLC cells than in BEAS-2E cells. Upregulation of miR-124 expression levels in both A549 and NCL-H460 cells by transfection with miR-124 mimics suppressed cell proliferation and induced apoptosis. Further investigation revealed that miR-124 bound directly to the 3' UTR region of STAT3, thereby inhibiting STAT3 expression. In addition, miR-124 levels detected in NSCLC tissues were lower than those in adjacent normal lung tissues, while the opposite was observed for STAT3. In NSCLC, the expression levels of miR-124 and STAT3 correlated significantly with the tumor node metastases (TNM) stage, differentiation grade and lymph node metastasis, while the levels of these molecules did not differ significantly by gender, age, location, smoking index, pleural invasion or pathological type. The expression level of miR-124 was significantly associated with disease-free survival (DFS) in both positive and negative lymph node groups. Furthermore, patients with low miR-124 or high STAT3 expression generally received a worse prognosis in terms of both overall survival (OS) and DFS. In conclusion, our findings suggest that miR-124 functions as a tumor suppressor by targeting STAT3, and that miR-124 may potentially serve as a useful biomarker for the prognosis of NSCLC patients.
本研究的目的是探讨miR-124在肺癌中的作用，并确定miR-124在非小细胞肺癌（NSCLC）患者术后的潜在预测价值。我们检测了A549、NCL-H460和正常肺上皮BEAS-2E细胞中miR-124的表达，结果显示NSCLC细胞中miR-124的表达水平显著低于BEAS-2E细胞。通过转染miR-124模拟物上调A549和NCL-H460细胞中miR-124的表达水平可抑制细胞增殖并诱导凋亡。进一步研究发现，miR-124直接与STAT3的3'UTR区域结合，从而抑制STAT3的表达。此外，NSCLC组织中检测到的miR-124水平低于相邻正常肺组织，而STAT3则相反。在NSCLC中，miR-124和STAT3的表达水平与肿瘤淋巴结转移（TNM）分期、分化程度和淋巴结转移显著相关，而这些分子的水平在性别、年龄、位置、吸烟指数、胸膜侵犯或病理类型方面无显著差异。miR-124的表达水平与阳性和阴性淋巴结组的无病生存期（DFS）均显著相关。此外，miR-124低表达或STAT3高表达的患者在总生存期（OS）和DFS方面通常预后较差。总之，我们的研究结果表明，miR-124通过靶向STAT3发挥肿瘤抑制作用，并且miR-124可能潜在地作为NSCLC患者预后的有用生物标志物。
