Mutant MEG3 Enhances the Activity of Telomerase by Increasing DNA Damage Repair in Human Liver Cancer Stem Cells

Abstract

Background: Long noncoding RNAs have recently considered as central regulators in diverse biological processes and emerged as vital players controlling tumorigenesis. Although wild MEG3 acts as a suppressor in several cancers, the function of mutant MEG3 is also unclear during tumorigenesis.Methods: Lentivalus infection,RT-PCR,Western blotting and tumorigenesis test in vitro and in vivo were performed.Results: our results suggest that mutant MEG3 promotes the growth of human liver cancer stem cells in vivo and in vitro.Mechanistically, our results show that mutant MEG3 enhances acetylation modification of HistoneH4 on K16.Then, mutant MEG3 enhances the expression of SETD2 dependent on H4K16Ac.Moreover, mutant MEG3 increases the DNA damage repair through SETD2.Ultimately, mutant MEG3 increases the telomeras activity dependent on DNA damage repair.Strikingly,TERT determines the cancerous function of mutant MEG3 in liver cancer stem cells. Therefore, we shed light on the fact that targeting mutant MEG3 could be a viable approach for cancer treatment.Conclusions: these observations will play an important role in finding effective tumor treatment targets.