miR-193a-3p及其潜在靶标星形胶质细胞上调基因-1在非小细胞肺癌组织中的表达及临床病理意义
Expression and clinicopathological significance of miR-193a-3p and its potential target astrocyte elevated gene-1 in non-small lung cancer tissues.
作者信息
Ren Fanghui, Ding Hua, Huang Suning, Wang Hanlin, Wu Mei, Luo Dianzhong, Dang Yiwu, Yang Lihua, Chen Gang
机构信息
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021 Guangxi Zhuang Autonomous Region People's Republic of China.
Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021 Guangxi Zhuang Autonomous Region People's Republic of China.
出版信息
Cancer Cell Int. 2015 Aug 7;15:80. doi: 10.1186/s12935-015-0227-8. eCollection 2015.
BACKGROUND
Aberrant expression of miR-193a-3p and astrocyte elevated gene-1 (AEG-1) have been revealed to be related to the tumorigenesis of various cancers, including non-small cell lung cancer (NSCLC). However, the significance of miR-193a-3p and its correlation with AEG-1 in NSCLC has not been explored. The purpose of this study was to evaluate the association between miR-193a-3p and AEG-1 and their relationship with the clinicopathological features in NSCLC patients.
METHODS
Via online in silico prediction, complementary sequences were found between miR-193a-3p and the 3'-untranslated region of AEG-1. Three independent cohorts were applied in the current study. Firstly, miR-193a-3p level was detected in 125 cases of NSCLC with quantitative real-time PCR (qRT-PCR). Secondly, AEG-1 protein level was evaluated in 339 cases of lung cancers with immunohistochemistry. Finally, the relationship between miR-193a-3p and AEG-1 protein expression was verified in another group with 65 cases of NSCLC.
RESULTS
The results showed that miR-193a-3p level was decreased in NSCLC tissues and significantly negatively related to tumor size (r = -0.277, P = 0.002), clinical TNM stage (r = -0.226, P = 0.011), lymph node metastasis (r = -0.186, P = 0.038), epidermal growth factor receptor (EGFR) protein level (r = -0.272, P = 0.041). On the contrary, AEG-1 protein expression was up-regulated in NSCLC and positively relative to tumor size (r = 0.240, P < 0.001), TNM stages (r = 0.164, P = 0.002) and lymph node metastasis (r = 0.232, P < 0.001) in NSCLC patients. In addition, miR-193a-3p was found to be inversely associated with AEG-1 protein expression in the third cohort (r = -0.564, P < 0.001).
CONCLUSION
In conclusion, miR-193a-3p and AEG-1 might be responsible for the carcinogenesis and aggressiveness of NSCLC. AEG-1 has the potential to be one of the targeted genes of miR-193a-3p. However, future in vitro and in vivo experiments are needed to verify this hypothesis.
背景
已发现miR-193a-3p和星形胶质细胞上调基因1（AEG-1）的异常表达与包括非小细胞肺癌（NSCLC）在内的多种癌症的肿瘤发生有关。然而，miR-193a-3p在NSCLC中的意义及其与AEG-1的相关性尚未得到探索。本研究的目的是评估miR-193a-3p与AEG-1之间的关联及其与NSCLC患者临床病理特征的关系。
方法
通过在线计算机模拟预测，在miR-193a-3p与AEG-1的3'-非翻译区之间发现了互补序列。本研究应用了三个独立的队列。首先，采用定量实时PCR（qRT-PCR）检测125例NSCLC患者的miR-193a-3p水平。其次，用免疫组织化学法评估339例肺癌患者的AEG-1蛋白水平。最后，在另一组65例NSCLC患者中验证miR-193a-3p与AEG-1蛋白表达之间的关系。
结果
结果显示，NSCLC组织中miR-193a-3p水平降低，且与肿瘤大小（r = -0.277，P = 0.002）、临床TNM分期（r = -0.226，P = 0.011）、淋巴结转移（r = -0.186，P = 0.038）、表皮生长因子受体（EGFR）蛋白水平（r = -0.272，P = 0.041）显著负相关。相反，NSCLC患者中AEG-1蛋白表达上调，且与肿瘤大小（r = 0.240，P < 0.001）、TNM分期（r = 0.164，P = 0.002）和淋巴结转移（r = 0.232，P < 0.001）呈正相关。此外，在第三个队列中发现miR-193a-3p与AEG-1蛋白表达呈负相关（r = -0.564，P < 0.001）。
结论
总之，miR-193a-3p和AEG-1可能与NSCLC的致癌作用和侵袭性有关。AEG-1有可能成为miR-193a-3p的靶基因之一。然而，未来需要进行体外和体内实验来验证这一假设。
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