| First Author | Liu Y | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4429 |
| PubMed ID | 30356100 | Mgi Jnum | J:267817 |
| Mgi Id | MGI:6267808 | Doi | 10.1038/s41467-018-06841-7 |
| Citation | Liu Y, et al. (2018) Nuclear lactate dehydrogenase A senses ROS to produce alpha-hydroxybutyrate for HPV-induced cervical tumor growth. Nat Commun 9(1):4429 |
| abstractText | It is well known that high-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and E7 was identified as one of the key initiators in HPV-mediated carcinogenesis. Here we show that lactate dehydrogenase A (LDHA) preferably locates in the nucleus in HPV16-positive cervical tumors due to E7-induced intracellular reactive oxygen species (ROS) accumulation. Surprisingly, nuclear LDHA gains a non-canonical enzyme activity to produce alpha-hydroxybutyrate and triggers DOT1L (disruptor of telomeric silencing 1-like)-mediated histone H3K79 hypermethylation, resulting in the activation of antioxidant responses and Wnt signaling pathway. Furthermore, HPV16 E7 knocking-out reduces LDHA nuclear translocation and H3K79 tri-methylation in K14-HPV16 transgenic mouse model. HPV16 E7 level is significantly positively correlated with nuclear LDHA and H3K79 tri-methylation in cervical cancer. Collectively, our findings uncover a non-canonical enzyme activity of nuclear LDHA to epigenetically control cellular redox balance and cell proliferation facilitating HPV-induced cervical cancer development. |
