Wang Xiaoying, Liu Yanli, Liu Xiaoli, Yang Jingyan, Teng Guoxin, Zhang Lulu, Zhou Chengjun
Department of Pathology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Provincial Key Laboratory of Radio-Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China.
Oncol Rep. 2016 May;35(5):3115-21. doi: 10.3892/or.2016.4648. Epub 2016 Mar 3.
Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In the present study, we detected miR-124 and SOX9 expression in lung ADC tissues. The results showed that miR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of miR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of miR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative miR-124 binding site in the 3' untranslated region (3'UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of miR-124. Furthermore, overexpression of miR-124 repressed SOX9 expression, whereas inhibition of miR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of miR-124 in A549 cells. Taken together, our results suggest that miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for miR‑based therapy against lung ADC.
越来越多的证据表明，微小RNA（miRNA）失调可能与癌症的发生和发展有关。然而，miR-124在肺腺癌（ADC）中的作用以及miR-124发挥其功能的潜在机制尚未完全明确。在本研究中，我们检测了肺ADC组织中miR-124和SOX9的表达。结果显示，与相应的非癌性肺组织相比，肺ADC组织中miR-124显著下调，且SOX9蛋白水平与miR-124的表达呈负相关。在人肺ADC细胞系A549中的研究表明，miR-124的上调可抑制细胞增殖、迁移和侵袭。生物信息学分析显示，SOX9的3'非翻译区（3'UTR）存在一个假定的miR-124结合位点。通过荧光素酶报告基因检测，我们验证了SOX9是miR-124的直接靶点。此外，miR-124的过表达抑制了SOX9的表达，而miR-124的抑制则增加了A549细胞中SOX9的表达。最后，我们确定SOX9是A549细胞中miR-124的功能介质。综上所述，我们的结果表明，miR-124通过直接靶向SOX9在肺ADC中发挥肿瘤抑制作用，它可能是基于miR的肺ADC治疗的有希望的候选者。
