TSGA10 and H2AX competition over binding HIF-1 in breast cancer

Abstract

Abstract Background HIF-1 stability and activity is known to be regulated by different factors such as TSGA10 and H2AX. Although TSGA10 and H2AX effects on the HIF-1 have already been demonstrated, changes in HIF-1 activity in the presence of both the mentioned factors are still not determined. So, in the current study we aimed to investigate HIF-1 activity by evaluation of metastasis and metabolism of breast cancer cells, in the presence of H2AX and TSGA10 over-expression. Methods TSGA10 vector was designed and stably transfected into MCF-7 cells. The efficiency of transfection was assessed by real-time PCR and western blot. After HIF-1 induction at high and low glucose conditions, cell proliferation, cell cycle profile, metabolic and metastasis activity of cells were assessed. Furthermore, biomarker expressions of ER, PR, HER2, Ki67, and E-cadherin in cancer cells were measured. Docking analysis was done for comparison and approval of TSGA10 and H2AX binding affinity to HIF-1. Results Increased expression of TSGA10 decrease the metastasis and metabolism activity in MCF-7. Docking analysis revealed that the binding affinity of TSGA10 to HIF-1 was greater than that of H2AX which confirms the earlier mentioned results. Conclusion Our findings indicated that TSGA10 over-expression decreased metastasis and metabolic activity of cancer cells through inhibiting H2AX impact on HIF-1 activity. Therefore, TSGA10 could be considered in the research for therapeutic candidates in cancer.