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Recent studies demonstrate that the invasion and metastasis of gastric cancer (GC) is closely associated with a multi-subunit vacuolar H+-ATPase (V-ATPase). Here we investigated the expression and role of the human  ATP6V1A  gene that encodes the catalytic subunit A of V-ATPase in GC. We found that  ATP6V1A  expression level is significantly elevated in GCs compared to normals, but GC patients with higher expression levels of  ATP6V1A  have a better prognosis. Genomic analysis revealed that  APT6V1A  copy number is gained in a small fraction of GC patients and lost in a minimum number. Moreover, the  ATP6V1A  copy number was positively correlated with its mRNA level. To explore additional mechanisms by which  ATP6V1A  overexpressed in GCs, we investigated the relationship between transcription factor YY1 and ATP6V1A, and found that mRNA expression of  YY1  had significant correlation with that of  ATP6V1A . To validate that YY1 transcriptionally regulates  ATP6V1A , we discovered that the  ATP6V1A  core promoter region contains three YY1 binding sites. Moreover, RNAi-mediated knockdown of YY1 in GC cells significantly decreased  ATP6V1A  mRNA and protein expression, while YY1 overexpression increased  ATP6V1A  expression level. In conclusion, YY1 may play an important regulatory role in  ATP6V1A  expression with potential mechanistic and clinical implications in GC.

Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers