Long noncoding RNA uc.263/264 cluster facilitates colorectal cancer progression by interacting with hnRNPK and activating The Wnt signaling pathway.

Colorectal cancer (CRC) represents a prevalent and life-threatening malignancy, posing a significant global health challenge. Transcribed ultraconserved regions (T-UCRs), a specific category of long non-coding RNAs (lncRNAs) encoded within the human genome, have been demonstrated to play significant roles in the pathogenesis of multiple cancer types. However, their pathological role in CRC remains largely unexplored. In this study, we investigate two closely spaced T-UCRs, uc.263 and uc.264, located on chromosome 9, both of which are significantly upregulated in CRC tissues. Our findings further reveal that these two T-UCRs originate from a shared precursor RNA, designated as uc.263/264 in CRC cells. The uc.263/264 has been demonstrated to enhance cellular proliferation, growth, migration, and invasion, while simultaneously regulating the cell cycle and apoptosis. Mechanistically, uc.263/264 interacts with heterogeneous nuclear ribonucleoprotein K (hnRNPK), enhancing its protein stability and resulting in increased hnRNPK expression. Furthermore, uc.263/264 activates the Wnt signaling pathway, a process mediated by hnRNPK. Clinically, both uc.263/264 and hnRNPK are overexpressed in CRC patient samples, exhibiting a positive correlation in their expression levels. This suggests a functional regulatory axis between uc.263/264 and hnRNPK in CRC pathology. Collectively, our findings demonstrate that uc.263/264 can interact with the hnRNPK protein and upregulate its expression, thereby activating the Wnt signaling pathway and promoting the progression of CRC.