HOXA5 is a tumor suppressor gene that is decreased in gastric cancer.

The abnormal expression of homeobox A5 (HOXA5) has been observed in breast and colon cancer; however, the clinical significance of HOXA5 in gastric cancer (GC) is not yet clear. In this study, we found that HOXA5 expression was decreased in GC tissues at the mRNA and protein level compared with paracancerous tissues using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis, respectively. Immunohistochemistry and Kaplan-Meier survival analysis confirmed that the underexpression of HOXA5 was associated with GC progression and indicated a poor prognosis of patients with GC. Given that proliferation-related genes may be potential target genes of HOXA5, we performed a series of experiments in vitro to examine the effects of HOXA5 on the proliferation of GC cells. A CCK-8 assay, colony formation assay and flow cytometry revealed that HOXA5 inhibited the abnormal proliferation of GC cells, and this finding was further supported by a 5-ethynyl-2-deoxyuridine (EdU) assay. Further mechanistic investigation clarified that HOXA5 promoted the protein expression of p21 and inhibited the protein expression of c-Myc and Ki67. Additionally, the use of nude mouse models also verified that HOXA5 suppressed the proliferation of GC cells in vivo. Collectively, the findings of this study demonstrate that HOXA5 acts as a tumor suppressor gene during the development and progresion of GC, possibly functioning by inhibiting the abnormal proliferation of cancer cells.