Methionine deficiency promoted mitophagy via lncRNA PVT1-mediated promoter demethylation of BNIP3 in gastric cancer

Background: The occurrence of recurrence and metastasis after treatment is a major challenge in the treatment of gastric cancer. This study was based on the methionine (Met)-dependent characteristics of gastric cancer cells to explore the effect of Met deficiency on the occurrence and development of gastric cancer. Methods: Human gastric cancer cell lines MKN45 and AGS and nude mice model were used to explore how Met affects gastric cancer by regulating lncRNA PVT1. Results: The levels of lncRNA PVT1 in gastric cancer cells and human gastric cancer xenografts of nude mice were down-regulated under the condition of Met deficiency. The cell viability and cell proliferation were declined after MKN45 and SGC-790 cells were cultured in Met-deficient medium. LncRNA PVT1 could affect BNIP3 promoter DNA methylation level through its interaction with DNMT1. Moreover, the silence of lncRNA PVT1 and the up-regulation of BNIP3 level inhibited the gastric cancer cell proliferation. Met deficiency could up-regulate BNIP3 expression by inhibiting the binding of lncRNA PVT1 to DNMT1, and activate mitophagy, thus inhibiting gastric cancer cell proliferation. Conclusion: Our study suggested that Met deficiency could down-regulate the expression of lncRNA PVT1, further demethylated the promoter of BNIP3, thus inhibiting the proliferation of gastric cancer cells by activating mitophagy.

Automated summary

The study showed that under conditions of Met deficiency, the down-regulation of lncRNA PVT1 further demethylates the promoter of BNIP3, inhibiting the proliferation of gastric cancer cells by activating mitophagy.