| Objective MicroRNA-24(miR-24) may involve 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 testedmiR-24expression in207pathology-diagnosed HCC cases from high AFB1exposure areas and HCC cells to explore whether miR-24expression in the HCCmodifies the pathological features ans prognosis of HCC.Methods (1) A total of207patients with I-II TNM-stage HCC wererecruited in this study. The corresponding surgical resection samples, includingtumor samples and adjacent non-cancerous tissue samples (at least5cm fromthe margin of the tumor), of all cases were collected for the following test andanalysis.(2) MiR-24expression levels in the tissue samples (including tumor tissuesand nonmalignant adjacent tissues of HCC) and cells (including liver cancer celllines and non-cancer liver cell line QSG-7701) were tested by TaqMAN-PCRtechnique. The amount of AFB1-DNA adducts in cancerous tissues samples wereevaluated by means of competitive enzyme-linked immunosorbent assay(ELISA). In this study, we elucidated AFB1exposure levels through the levels of AFB1-DNA adducts.(3) We collected demographic information (including sex, age, ethnicity,hepatitis B virus and hepatitis C virus infection) and clinical pathological data(including cirrhosis, tumor size, tumor differentiation, and tumor stage), andfollowed all HCC cases for survival analysis. Cox’s regression model andlogistic regression model were used to analyze the relationship between miR-24expression and HCC pathological features and prognosis.(4) The functional role of miR-24in HCC tumorigenesis was evaluated bycell proliferation and apoptosis analysis.(5) Both HCC samples analysis and toxin experiments of AFB1in vitro wereused to elucidate the effects of miR-24expression on AFB1-DNA formationResults (1) High AFB1exposure level was associated with decreasing1-year,3-year, and5-year survival rate. This variable increased dying risk and tumorreoccurring risk of HCC, with a HR of2.12(95%CI=1.46-3.08, P <0.01) and2.40(95%CI=1.49-3.88, P <0.01), respectively. These results suggest thatAFB1exposure levels should modify the outcome of HCC.(2) We found that miR-24expression was significantly higher in tumourtissues (TT) than in non-malignant adjacent liver tissues (NT), and similarresults were also observed in the cancer cells analysis in vitro.（3）High miR-24expression modified the overall survival (HR=3.58,95%CI=2.34-5.46) and recurrence-free survival (HR=4.75,95%CI=2.66-8.47)of HCC patients.（4）High miR-24expression was associated with larger tumor size (OR=2.01), higher MVD (OR=2.63), and lower tumor differentiation (OR=2.10),suggesting that the levels of MiR-24expression might exhibit effects on theclinic-pathological features of HCC patients. （5）Overexpression of miR-24in HCC cells promoted tumor cellproliferation and decreased tumor cell apoptosis; whereas downregulation ofmiR-24inhibited tumor cell proliferation, and promoted tumor cell apoptosis.（6）The toxic experiments ofAFB1showed that the overexpression ofmiR-24progressed the formation of AFB1-DNA adducts in vitro, and similarresults were also found in the analysis of HCC samplesConclusion These results suggest that miR-24expression might modulatethe prognosis of AFB1-related HCC, and be involved in HCC tumorigenesis. Itmay be a potential therapeutic targets for HCC, especially from high AFB1exposure areas. |
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