ANKRD62 Modulates NF-κB Signaling to Promote Proliferation and Migration in UCEC.

Members of the ankyrin repeat domain (ANKRD) family are involved in multiple cellular functions, including cell cycle regulation, cell adhesion, and signaling, and have been implicated in the pathogenesis of various cancers. However, the function of ANKRD62, a recently identified member of this family, remains largely unexplored. This study investigated the clinical significance and biological function of ANKRD62 in uterine corpus endometrial carcinoma (UCEC). Through gene expression profiling, we identified ANKRD62 upregulation in UCEC tissues compared to paired adjacent normal tissues. Using overexpression and shRNA-mediated knockdown in cell lines and mouse models, we demonstrated that ANKRD62 is significantly upregulated in UCEC tissues, with expression levels positively correlated with tumor grade and inversely associated with patient survival. In vitro functional assays revealed that ANKRD62 overexpression markedly enhanced UCEC cell proliferation and migration, whereas ANKRD62 knockdown suppressed these malignant phenotypes without significantly affecting apoptosis. Consistent with these findings, in vivo experiments showed that ANKRD62-overexpressing cells exhibited accelerated tumor growth and increased metastatic potential. Mechanistically, ANKRD62 was found to be associated with NF-κB pathway modulation, promoting p65 nuclear translocation and phosphorylation, thereby affecting cellular function. In summary, this study provides the first evidence that ANKRD62 acts as a critical oncogenic driver in UCEC progression and unveils its functional association with NF-κB signaling. These findings highlight the potential of ANKRD62 as a novel therapeutic target and offer new insights into the molecular mechanisms underlying UCEC pathogenesis.