人肝细胞癌中PCNA和RAB10水平上调miR-224表达下调

Upregulation of PCNA and RAB10 level and downregulation of miR-224 expression in human hepatocellular carcinoma

目的为了进一步揭示肝癌发生的分子机理,探讨肝癌中细胞增殖与miR-224、RAB10表达之间的关系。方法选取确诊的肝细胞癌患者8例,手术后分别获得其肝细胞癌和癌旁组织,免疫组织化学检测代表细胞增殖的PCNA和癌基因产物RAB10的表达,实时定量PCR检测miR-224的表达。结果在肝细胞癌中,细胞增殖水平非常显著地高于癌旁组织;miR-224表达显著地低于癌旁组织,但RAB10水平显著高于癌旁组织。结论肝细胞癌发生可能在于肝细胞中下调的miR-224对其靶基因rab10沉默作用降低,使其高水平表达RAB10;高水平RAB10作为细胞癌基因产物促进细胞的增殖、发生肝癌。

Objective To reveal the molecular mechanism of liver carcinogenesis, and to explore the relationship between cell proliferation and the expression of miR-224 and RAB10 in liver cancer. Methods The liver cancer and cancer adjacent tissues were individually obtained from eight patients with hepatocellular carcinoma after operation. PCNA expression that represented cell proliferation and oncogene product RAB10 were detected by the 2-step immunohistochemical method. Expression of miR-224 was determined by real-time quantitative PCR. Results The level of cell proliferation in the liver cancer was remarkably higher than that in cancer adjacent tissue. The expression of miR-224 in the cancer was decreased obviously, but the level of RAB10 was remarkably higher than that in the cancer adjacent tissue. Conclusion Hepatocellular carcinogenesis may be involved in the reduced silencing effect of down-regulated miR-224 in hepatocytes on its target gene rab10, thereby resulting in high-level expression of RAB10. High-level of RAB10 as a cell oncogene product promotes cell proliferation and hepatocarcinogenesis.