Using DAVID, we found that hypermethylated genes in ESC cells are mostly enriched with the regulation of cell cycle (FZR1, E2F5, BOP1, TRRAP, CDK4, JUNB, etc.), cell death (SIVA1, MCL1, YPEL3, ARF6, UBQLN1, SHF, CIAPIN1, APLP1, GPX1, CASP3, etc.), and mRNA metabolic process (SCAF1, FIP1L1, STRAP, RBM15B, CWC15, XAB2, YBX1, AUH, SF3B2, APLP1, HNRNPL, etc.); the hypomethylated genes are enriched with functions related to ATP synthesis (ATP6V1F, ATP6V1C1
, ATP6V0C, ATP6V1A, ATP6V0E, ATP6V1E1, ATP5C1, etc.) and mitochondrial ribosome (MRPL15, MRPL27, MRPL16, MRPL36, MRPL39, MRPL34, DAP3, etc.) (Excel Sheet S2).
It encodes a vacuolar component of ATPase (V-ATPase) (Curtis and Kane 2002), an enzyme multisubunit that mediates the acidification of eukaryotic intracellular organelles (27) ATP6V1C1 and ATP6V1C2 a and b, two alternative transcript variants encoding different isoforms, have been identified in this gene.
Our research group has found that ATP6V1C1 levels were significantly higher in patients with OSCC than in healthy controls, with expression increasing with higher tumor stage.
Intracellular pH regulation in oral squamous cell carcinoma is mediated by increased V-ATPase activity via over-expression of the ATP6V1C1 gene.