Liu Yi-Xiao, Long Xi-Dai, Xi Zhi-Feng, Ma Yun, Huang Xiao-Ying, Yao Jin-Guang, Wang Chao, Xing Tian-Yu, Xia Qiang
Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Road, No. 1630, Shanghai 200127, China.
Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Road, No. 1630, Shanghai 200127, China ; Department of Pathology, Youjiang Medical College for Nationalities, Baise 533000, China.
Biomed Res Int. 2014;2014:482926. doi: 10.1155/2014/482926. Epub 2014 Apr 8.
MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66-8.47) and overall survival (HR = 3.58, 95% CI = 2.34-5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.
微小RNA-24(miR-24)可能参与肿瘤形成过程;然而,这种微小RNA在与黄曲霉毒素B1(AFB1)相关的肝细胞癌(HCC)中的作用尚未得到充分阐述。在此,我们检测了来自高AFB1暴露地区的207例经病理诊断的HCC病例以及HCC细胞中miR-24的表达。我们发现,相对于相邻的非癌组织样本,miR-24在HCC肿瘤组织中上调,并且miR-24的高表达与更大的肿瘤大小、更高的微血管密度和肿瘤去分化显著相关。此外,这种微小RNA的过表达改变了HCC患者的无复发生存率(相对风险比[HR],4.75;95%置信区间[CI],2.66 - 8.47)和总生存率(HR = 3.58,95% CI = 2.34 - 5.46)。此外,我们观察到一些miR-24与AFB1暴露对HCC预后联合作用的证据。在功能上,miR-24过表达促进肿瘤细胞增殖,抑制细胞凋亡,并促进AFB1 - DNA加合物的形成。这些结果首次表明,miR-24可能改变与AFB1相关的HCC预后和肿瘤发生。