College of Pharmacy, Nanchang University, Nanchang, Jiangxi, P.R. China.
The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, P.R. China.
PLoS One. 2018 Dec 14;13(12):e0207139. doi: 10.1371/journal.pone.0207139. eCollection 2018.
Tumor suppressor genes (TSGs), including Ten-eleven translocation 1 (TET1), are hypermethylated in hepatocellular carcinoma (HCC). TET1 catalytic domain (TET1-CD) induces genome-wide DNA demethylation to activate TSGs, but so far, anticancer effects of TET1-CD are unclear. Here we showed that after HCC cells were transiently transfected with TET1-CD, the methylation levels of TSGs, namely APC, p16, RASSF1A, SOCS1 and TET1, were distinctly reduced, and their mRNA levels were significantly increased and HCC cells proliferation, migration and invasion were suppressed, but the methylation and mRNA levels of oncogenes, namely C-myc, Bmi1, EMS1, Kpna2 and c-fos, were not significantly change. Strikingly, HCC subcutaneous xenografts in nude mice remained to be significantly repressed even 54 days after transient transfection of TET1-CD. So, transient transfection of TET1-CD may be a great advance in HCC treatment due to its activation of multiple TSGs and persistent anticancer effects.
抑癌基因（TSGs），包括 Ten-eleven translocation 1（TET1），在肝细胞癌（HCC）中呈高甲基化状态。TET1 催化结构域（TET1-CD）诱导全基因组 DNA 去甲基化以激活 TSGs，但迄今为止，TET1-CD 的抗癌作用尚不清楚。在这里，我们发现 HCC 细胞瞬时转染 TET1-CD 后，TSGs（即 APC、p16、RASSF1A、SOCS1 和 TET1）的甲基化水平明显降低，其 mRNA 水平显著升高，HCC 细胞增殖、迁移和侵袭受到抑制，但癌基因（即 C-myc、Bmi1、EMS1、Kpna2 和 c-fos）的甲基化和 mRNA 水平没有明显变化。值得注意的是，即使在瞬时转染 TET1-CD 54 天后，裸鼠 HCC 皮下异种移植仍然受到显著抑制。因此，由于 TET1-CD 可激活多个 TSGs 并持续发挥抗癌作用，因此其对 HCC 的治疗可能是一个重大进展。
