Zhang Mingxin, Yang Qi, Zhang Lingmin, Zhou Suna, Ye Wenguang, Yao Qinglin, Li Zongfang, Huang Cheng, Wen Qinsheng, Wang Jingjie
Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038 Shaanxi Province, China.
J Exp Clin Cancer Res. 2014 Jan 19;33(1):10. doi: 10.1186/1756-9966-33-10.
ErbB4 expression has been noted in various tumors, but its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate whether miR-302b regulates the expression of ErbB4 at the post-transcriptional level and to determine its expression, significance, and function in ESCC.
We used real-time reverse transcriptase-polymerase chain reaction to quantify the expression of miR-302b in 50 ESCC tissues and analyzed its relationship with clinicopathological factors and survival. Then, we investigated the post-transcriptional regulation of ErbB4 expression using immunoblot analysis and luciferase reporter assays. Finally, the effects of miR-302b on proliferation, apoptosis, and invasion of ESCC cells was detected using MTT, flow cytometric analysis, and transwell invasion assays, respectively.
miR-302b was significantly down-regulated and correlated with tumor differentiation and lymph node metastasis in ESCC. Univariate and multivariate analyses indicated that low miR-302b expression might be a poor prognostic factor. Further studies demonstrated that miR-302b post-transcriptionally down-regulated the expression of ErbB4 in vitro. Moreover, miR-302b inhibited proliferation by inducing apoptosis and repressed invasion in the ESCC cell lines.
miR-302b is a potential molecular marker of ESCC and functions as a tumor suppressor by post-transcriptionally regulating ErbB4.
在多种肿瘤中已发现ErbB4表达,但它在食管鳞状细胞癌(ESCC)中的调控机制仍不清楚。本研究旨在探讨miR-302b是否在转录后水平调节ErbB4的表达,并确定其在ESCC中的表达、意义及功能。
我们采用实时逆转录聚合酶链反应定量50例ESCC组织中miR-302b的表达,并分析其与临床病理因素及生存的关系。然后,我们使用免疫印迹分析和荧光素酶报告基因检测来研究ErbB4表达的转录后调控。最后,分别采用MTT法、流式细胞术分析和Transwell侵袭实验检测miR-302b对ESCC细胞增殖、凋亡及侵袭的影响。
miR-302b在ESCC中显著下调,且与肿瘤分化及淋巴结转移相关。单因素和多因素分析表明,低miR-302b表达可能是一个不良预后因素。进一步研究表明,miR-302b在体外转录后下调ErbB4的表达。此外,miR-302b通过诱导凋亡抑制增殖,并抑制ESCC细胞系的侵袭。
miR-302b是ESCC的潜在分子标志物,通过转录后调节ErbB4发挥肿瘤抑制作用。