DNMT3B and TET1 mediated DNA methylation of LATS1 regulates BC progression via hippo signaling pathway

Background: Large tumor suppressor gene 1 (LATS1) is one of the key proteins in the Hippo signaling pathway, which plays a role in inhibiting tumor progression, but its anti-tumor role in tumors is inhibited. Nevertheless, the specific molecular mechanism of its role in breast cancer (BC) are still unclear.

Methods: The expression of LATS1 in BC was detected by RT-qCR and WB. The biological effect of LATS1 on BC was verified in vitro and in vivo. DNA methylation sequencing and MSP were used to detect the effect of DNMT3B and TET1 on LATS1 methylation. Analysis of the effect of DNMT3B and TET1 on the biological behavior of BC cells via LATS1 by cell function experiment.

Results: Results indicated that the expression of LATS1 is lower in BC tumor tissues and BC cell lines. low LATS1 expression BC patients have a shorter overall survival. Increasing LATS1 expression can inhibit the proliferation, migration and invasion of BC. LATS1 found to have high DNA methylation changes in the promoter region. Moreover, DNMT3B was increased in BC tissues, and DNA demethylase TET1 was decreased in BC tissues. Furthermore, DNMT3B and TET1 regulate the methylation of LATS1, and methylation of LATS1 inactivates Hippo signaling pathway.

Conclusion: Our results indicate that the methylation of LATS1 is regulated by DNMT3B and TET1 and regulates its protein expression and the function of Hippo signaling pathway.