Lv Jun, Yu Ya-Qun, Li Shu-Qun, Luo Liang, Wang Qian
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China E-mail :
Asian Pac J Cancer Prev. 2014;15(6):2565-70. doi: 10.7314/apjcp.2014.15.6.2565.
H19 is an imprinted oncofetal gene, and loss of imprinting at the H19 locus results in over-expression of H19 in cancers. Aflatoxin B1(AFB1) is regarded as one of the most dangerous carcinogens. Exposure to AFB1 would most easily increase susceptibility to diseases such as hepatocellular carcinoma(HCC) but any possible relationship between AFB1 and H19 is not clear. In present study, we found that AFB1 could up-regulate the expression of H19 and promote cell growth and invasion by hepatocellular carcinoma HepG2 cells. Knocking down H19 RNA co ld reverse the effects of AFB1 on cell growth and invasion. In addition, AFB1 induced the expression of E2F1 and its knock-down could down-regulate H19 expression and suppress cell growth and invasion in hepatocellular carcinoma HepG2 cells. Furthermore, E2F1 over-expression could up-regulate H19 expression and promote cell growth and invasion, with binding to the H19 promoter being demonstrated by chromatin immunoprecipitation assays (ChIP). In summary, our results suggested that aflatoxin B1 could promote cell growth and invasion in hepatocellular carcinoma HepG2 cells through actions on H19 and E2F1.
H19是一种印记癌胚基因，H19基因座的印记缺失会导致H19在癌症中过度表达。黄曲霉毒素B1（AFB1）被认为是最危险的致癌物之一。接触AFB1最容易增加患肝细胞癌（HCC）等疾病的易感性，但AFB1与H19之间的任何可能关系尚不清楚。在本研究中，我们发现AFB1可以上调H19的表达，并促进肝癌HepG2细胞的生长和侵袭。敲低H19 RNA可以逆转AFB1对细胞生长和侵袭的影响。此外，AFB1诱导E2F1的表达，敲低E2F1可以下调肝癌HepG2细胞中H19的表达并抑制细胞生长和侵袭。此外，E2F1的过表达可以上调H19的表达并促进细胞生长和侵袭，染色质免疫沉淀分析（ChIP）证明E2F1与H19启动子结合。总之，我们的结果表明，黄曲霉毒素B1可以通过作用于H19和E2F1促进肝癌HepG2细胞的生长和侵袭。
