Leucine-rich pentatricopeptide repeat-containing protein silencing transcriptionally regulated by GATA-binding protein 3 has an anti-glioma effect by regulating glycolysis and ferroptosis by mediating N6-methyladenosine modification of protocadherin-

Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is a recently identified N6-methyladenosine (m6A) reader protein involved in a myriad of biological processes in cancer. However, its roles in glioma have not been reported. Both in vitro and in vivo studies were performed to examine the anti-glioma activity of LRPPRC silencing. Chromatin immunoprecipitation assay and RNA immunoprecipitation assay were used for the analysis of interaction between upstream and downstream molecules. Methylated RNA immunoprecipitation assay was conducted to examine m6A modification. Our results showed that LRPPRC expression was dramatically upregulated in glioma tissues and cell lines. LRPPRC regulated the m6A modification of protocadherin-7 (PCDH7) and affected its expression in glioma cell lines; LRPPRC silencing significantly inhibited glycolysis and induced ferroptosis in glioma cell lines; this was reversed by PCDH7 overexpression. Furthermore, GATA-binding protein 3 (GATA3) directly bound to the LRPPRC promoter and transcriptionally regulated LRPPRC. LRPPRC mediated the regulatory effects of GATA3 on glycolysis and ferroptosis in glioma cell lines. In vivo studies showed that LRPPRC silencing suppressed tumor growth. Taken together, our data demonstrate that LRPPRC expression was dramatically upregulated in gliomas and that inhibition of the GATA3/LRPPRC/PCDH7 axis exerted an anti-glioma effect by regulating glycolysis and ferroptosis.