FAM49B suppresses ovarian cancer cell growth through regulating MAPK signaling.

Abstract

Recently, the family with sequence similarity 49 member B (FAM49B, also called CYRI-B) has garnered attention as a new target in cancer development. FAM49B is upregulated in ovarian cancer tissues; however, its role and mechanism in ovarian cancer progression remain unknown. Herein, we demonstrated that FAM49B knockdown significantly increases ovarian cancer cell viability, EdU incorporation, and clonogenic growth. In contrast, the forced expression of FAM49B achieved opposite effects. Furthermore, an ovo model was used to assess the in vitro effects of FAM49B depletion or overexpression on the growth of ovarian cancer. In a xenograft model, we observed that FAM49B overexpression alleviated tumor formation. Transcriptomic analysis of FAM49B-depleted and control cells revealed that FAM49B silencing upregulated the MAPK pathway. Consistent with the transcriptomic analysis results, we noted that FAM49B knockdown enhanced EGFR activation and downstream MEK-ERK signaling; in contrast, FAM49B overexpression exhibited opposite trends. In addition, FAM49B played a role in EGF-induced sphere growth of ovarian cancer cells. Notably, treatment with the MEK inhibitor trametinib considerably impaired the increased cell growth by FAM49B knockdown in cell culture and ovo models. Collectively, our results suggest that FAM49B can suppress the growth of ovarian cancer cells by regulating the MAPK signaling pathway.