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Introduction
Gastric cancer is one of the most frequent causes of cancer-related deaths worldwide (1) and is the most commonly diagnosed cancer, ranking third in cancer mortality rates in Korea (2). Early diagnosis, improved nutritional care, and new chemotherapies have led to better outcomes over the past 20 years (3). However, chemotherapy has limited effects (4), and targeted therapy is used only for a small subset of patients due to restricted availability of biomarkers (5,6). Thus, studies of mechanisms contributing to gastric cancer are essential for development of new therapeutic strategies.
HOXC10 is a member of the HOX genes and contributes to hind limb development (7). In addition to its role as a developmental regulator, recent studies revealed additional roles of HOXC10, such as controlling the browning of white adipose tissues and regulation of the cell cycle (8,9). In addition, recent studies have reported aberrant expression of HOXC10 and its effects in diverse cancers. Studies in glioma, lung adenocarcinoma, osteosarcoma, and thyroid cancer demonstrated that aberrant HOXC10 expression was correlated with poor survival outcome (10–13). HOXC10 knockdown enhanced apoptosis and attenuated proliferation, metastasis, and expression of immunosuppressive genes in glioma (12). In thyroid cancer, HOXC10 knockdown was associated with cell cycle arrest and repression of metastasis (10). In breast cancer, HOXC10 was upregulated by estrogen, which recruits MLL3 and MLL4 to the estrogen response element in the HOXC10 promoter region (14). However, in breast cancer treated with aromatase inhibitors, resistance to the inhibitors occurred through downregulation of HOXC10 expression mediated by hypermethylation of HOXC10 promoter regions (15). Another study revealed that HOXC10 contributed to chemotherapy resistance through DNA repair by binding with cyclin-dependent kinase 7 and activating the NF-κB pathway (16). Collectively, HOXC10 plays roles as a transcription factor in the development and in cancer progression. Moreover, HOXC10 mediates additional functions by binding to other proteins.
Epigenetic alterations, including DNA methylation, histone modification and non-coding RNAs, are as important as genetic mutations in cancer progression and metastasis (17). DNA methylation of promoter CpG islands interrupts binding of transcription factors, thus, repressing gene expression (18). In cancer, numerous tumor suppressor genes are downregulated by hypermethylation, while oncogenes are upregulated by hypomethylation, at their CpG promoter sites (17,18).
Recent studies have reported that HOXC10 is...