HMGA2 is down-regulated by microRNA let-7 and associated with epithelial-mesenchymal transition in oesophageal squamous cell carcinomas of Kazakhs

摘要

Aims: To investigate the expression of let-7 and its regulation of high-mobility group A2 protein (HMGA2), and to verify the relationship between let-7, HMGA2 and the process of epithelial-mesenchymal transition (EMT), in oesophageal squamous cell carcinomas (OSCC) of Kazakh patients. Methods and results: Expression of let-7 was significantly lower in EcalO9 cells than in normal oesophageal squamous epithelium (P = 2.4 x 10~7). Increased accumulation of let-7 after transfection of Ecal09 cells with synthetic let-7 inhibited cell proliferation. Let-7 could repress expression of HMGA2 after co-transfection with let-7 and HMGA2 (P = 0.002). Moreover, let-7 expression was observed less frequently (P = 2.0 x 10~8), and HMGA2 expression more fre-quently (P = 1.0 x 10"10), in OSCC than in normal adjacent tissues; and let-7 expression was observed less frequently in OSCC from Kazakh patients than in those from Han and Uygur patients (P = 0.041). There was a reverse correlation between expression of let-7 and HMGA2 (P = 0.018). Expression of Snail was statistically higher in Kazakhs' OSCC (P = 0,029), and was correlated with depth of invasion (P = 0.021) and HMGA2 expression (P = 0.026). Conclusions: Expression of let-7 can suppress cell proliferation by acting directly on regulation of HMGA2 in OSCC. High expression of Snail and its correlation with HMGA2 expression and tumour invasion suggest that HMGA2 may be involved in EMT in the OSCC of Kazakh patients.