Unveiling the oncogenic function of CCDC12 in regulating RBM47 splicing in breast cancer.

Breast cancer (BC) remains a leading cause of cancer-related mortality, in part due to the lack of effective therapeutic targets. In this study, we report that Coiled-Coil Domain Containing 12 (CCDC12), a relatively uncharacterized member of the CCDC protein family, is upregulated in BC tissues. Functional assays in vitro and in vivo indicate that CCDC12 contributes to malignant phenotypes, including enhanced proliferation and metastatic potential. Transcriptomic analysis is associated with widespread alterations in alternative splicing programs. Among the affected events, RNA Binding Motif Protein 47 (RBM47) was identified as a splicing-related target exhibiting increased exon 5 skipping following CCDC12 knockdown. This splicing change produces a truncated RBM47 isoform with reduced tumor-suppressive activity, while reintroduction of full-length RBM47 partially restores impaired cellular phenotypes. These findings support the existence of a CCDC12-RBM47 regulatory relationship that may participate in breast cancer progression, although the upstream signals and detailed molecular mechanisms remain to be clarified. Collectively, the study provides insight into a previously underappreciated role of CCDC12 in breast cancer biology and highlights the need for future work to establish its mechanistic and translational significance.