Qin Yi, Zhang Yi, Tang Qinting, Jin Li, Chen Yong'an
Department of Gastroenterology, First People's Hospital of Yancheng City, Yancheng 224001, China.
Department of Oncology, Jimin Hospital, Shanghai 200052, China.
Acta Biochim Biophys Sin (Shanghai). 2017 Feb 6;49(2):138-148. doi: 10.1093/abbs/gmw127.
Increasing evidence suggests that microRNAs, which control gene expression at the post-transcriptional level, are aberrantly expressed in cancers and play significant roles in carcinogenesis and cancer progression. In this study, we show differential miR-133b down-expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. In addition, squalene epoxidase (SQLE), a key enzyme of cholesterol synthesis, is identified as the direct downstream target gene of miR-133b by luciferase gene reporter assay. Furthermore, ectogenic miR-133b expression and SQLE knockdown can inhibit proliferation, invasion, and metastasis, and diminish epithelial-to-mesenchymal transition (EMT) traits of ESCC in vitro, implying that miR-133b-dependent SQLE can induce tumorigenicity and that SQLE is an EMT inducer. Xenograft experiment results also proved the biological function of SQLE in vivo. Therefore, we conclude that miR-133b-dependent SQLE plays a critical role in the potential metastasis mechanisms in ESCC.
越来越多的证据表明，在转录后水平控制基因表达的微小RNA（microRNA）在癌症中异常表达，并在致癌作用和癌症进展中发挥重要作用。在本研究中，我们发现人食管鳞状细胞癌（ESCC）细胞和组织中miR-133b存在差异性低表达。此外，通过荧光素酶基因报告基因检测，胆固醇合成的关键酶角鲨烯环氧酶（SQLE）被确定为miR-133b的直接下游靶基因。此外，外源性miR-133b表达和SQLE基因敲低可抑制ESCC体外的增殖、侵袭和转移，并减少上皮-间质转化（EMT）特征，这意味着miR-133b依赖的SQLE可诱导肿瘤发生，且SQLE是一种EMT诱导剂。异种移植实验结果也证实了SQLE在体内的生物学功能。因此，我们得出结论，miR-133b依赖的SQLE在ESCC潜在转移机制中起关键作用。
