Background: HOXA10 has been reported to be deregulated in many kinds of cancers including gastric cancer. But its role in gastric cancer progression is controversial. Therefore, the current study was performed to explore the role and mechanism of HOXA10 in gastric cancer.
Materials and methods: IHC and Western blotting assays were used to assess HOXA10 expression in gastric cancer tissues and cells. Lentivirus infection was used to alter HOXA10, STAT3 and JAK1 expression in gastric cancer NCI-N87 and MKN28 cells. MTT, cloning formation, flow cytometry and in vivo xenotransplantation experiments were carried out to assess cell proliferation, cloning formation, apoptosis and tumorigenesis.
Results: HOXA10 expression was obviously increased in gastric cancer tissues and cells when compared with the normal gastric tissue samples and cells. Upregulation of HOXA10 significantly enhanced cell proliferation, cloning formation and tumorigenesis abilities and reduced cell apoptosis in gastric cancer, and promoted the activation of JAK1/STAT3 signaling. In addition, we showed that the effects of HOXA10 on the promotion of cell viability and tumorigenesis and cell apoptosis repression were all weakened when JAK1 or STAT3 was downregulated.
Conclusion: This study demonstrates that HOXA10 functions as an oncogene in gastric cancer through activating JAK1/STAT3 signaling.
Keywords: HOXA10, JAK1/STAT3, viability, apoptosis, tumorigenesis, gastric cancer