The cancer-testis gene, sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency.

OBJECTIVE

The newly defined cancer-testis (CT) gene, was previously found to play key roles in DNA double-strand break (DSB) repair. In this study, we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers (TNBCs).

METHODS

The Cancer Genome Atlas database was used to quantify the expression of . Cox regression analysis was used to evaluate the association between expression and the prognosis of human TNBC. The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed . Patient-derived xenograft (PDX) models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.

RESULTS

We confirmed as a CT gene whose expression was restricted to the testes and breast tumors, especially TNBCs. Its activation was significantly associated with poor survival in breast cancer patients [overall, hazard ratio (HR) = 1.90 (1.16-2.06); TNBCs: HR = 7.05 (1.16-41.80)]. In addition, we found that was oncogenic and significantly promoted the proliferation of TNBC cells. Further analysis showed that participated in DSB repair in TNBCs. However, in contrast to its function in meiosis, it mediated homologous recombination deficiency (HRD) through the activation of polyADP-ribose polymerase (PARP)1 by interacting with YBX1. Furthermore, activated MEIOB was shown to confer sensitivity to PARP inhibitors, which was confirmed in PDX models.

CONCLUSIONS

played an oncogenic role in TNBC through its involvement in HRD. In addition, dysregulation of sensitized TNBC cells to PARP inhibitors, so may be a therapeutic target of PARP1 inhibitors in TNBC.