Homeodomain-containing gene 10 (
HOXC10
) is a member of the homeobox transcription factors that plays an important role in the development of multicellular organisms.
HOXC10
is overexpressed in a variety of human cancers, and recent studies have revealed that
HOXC10
is upregulated in gastric cancer as well. However, its mechanism of action is not fully understood, thus, the role of
HOXC10
was investigated in the present study in human gastric cancer. First,
HOXC10
expression was revealed to be significantly increased in gastric cancer tissues compared to normal tissues (TCGA dataset), and
HOXC10
upregulation was associated with decreased recurrence-free survival in gastric cancer patients in a public gene expression dataset.
HOXC10
promoted cell proliferation and metastasis in two gastric cancer cell lines (AGS and MKN74). Analyzing TCGA 450K DNA methylation dataset, it was revealed that
HOXC10
CpG sites were hypomethylated in gastric cancer tissues. Bisulfite sequencing revealed that CpG sites in the
HOXC10
first intronic region were hypomethylated in three gastric cancer tissues, and
HOXC10
expression was increased in gastric cancer cell lines (AGS and SNU620) in response to 5-azacytidine treatment. By RNA-sequencing of AGS cells with ectopic
HOXC10
expression, it was revealed that many genes were upregulated by
HOXC10
overexpression. Among them,
CST1
was predicted to be a
HOXC10
direct target gene via prediction of
HOXC10
binding sites from the JASPAR database. A chromatin immunoprecipitation assay revealed that
HOXC10
directly bound to
CST1
promoter regions. The present study proposes
HOXC10
is a potential prognostic marker or therapeutic target in human gastric cancer.