Cheng Lina, Yang Fan, Zhou Bingxi, Yang Hui, Yuan Yuan, Li Xiuling, Han Shuangyin
Department of Gastroenterology, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Henan Province, China.
Department of Gastroenterology, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Henan Province, China.
Gene. 2016 Dec 20;595(1):31-38. doi: 10.1016/j.gene.2016.09.028. Epub 2016 Sep 19.
RAB23, a member of Ras-related small GTPase family, has been reported to be up-regulated in several cancer types. However, its biological functions and the underlying molecular mechanisms for its oncogenic roles in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we have shown that the expression of RAB23 was elevated in ESCC tissues and ESCC cells. Overexpression of RAB23 promoted the growth and migration of the ESCC cells, while knocking down the expression RAB23 inhibited the growth, migration and metastasis of the ESCC cells. The molecular mechanism study showed that RAB23 activated beta-catenin/TCF signaling and regulated the expression of several target genes. In the further study, it was found that the expression of RAB23 was regulated by the miR-92b. Forced expression of MiR-92b decreased the mRNA and protein level of RAB23, and RAB23 rescued the biological functions of miR-92b. Taken together, this study revealed the oncogenic roles and the regulation of RAB23 in ESCC, suggesting RAB23 might be a therapeutic target.
RAB23是Ras相关小GTP酶家族的成员之一，据报道在几种癌症类型中表达上调。然而，其生物学功能以及在食管鳞状细胞癌（ESCC）中致癌作用的潜在分子机制仍不清楚。在本研究中，我们发现RAB23在ESCC组织和ESCC细胞中表达升高。RAB23的过表达促进了ESCC细胞的生长和迁移，而敲低RAB23的表达则抑制了ESCC细胞的生长、迁移和转移。分子机制研究表明，RAB23激活β-连环蛋白/TCF信号并调节多个靶基因的表达。在进一步的研究中，发现RAB23的表达受miR-92b调控。强制表达MiR-92b可降低RAB23的mRNA和蛋白水平，而RAB23可挽救miR-92b的生物学功能。综上所述，本研究揭示了RAB23在ESCC中的致癌作用及其调控机制，提示RAB23可能是一个治疗靶点。
