Identification of a novel lncRNA in pancreatic cancer: Contribution to malignancy through Wnt pathway regulation

Long non-coding RNAs (lncRNAs) are non-coding RNAs longer than 200 nucleotides that play essential roles in transcriptional regulation and protein localization through interactions with various proteins. These functions have attracted considerable attention in cancer research. We identified lnc243, which is highly expressed in mesenchymal-type cells of pancreatic ductal adenocarcinoma (PDAC) and is associated with poor patient survival. Previous studies reported that lnc243 regulates mRNA expression by acting as a competing endogenous RNA through binding to miRNAs. However, the subcellular localization of lnc243 and its function through protein interactions in PDAC remain poorly understood.RNA fluorescence in situ hybridization (RNA-FISH) revealed that lnc243 localization varies depending on the cellular state: it is localized to the cell membrane in adherent cells but translocates into the cytoplasm during invasion. Because lnc243 and beta-catenin were found to co-localize on the cell membrane, we next examined their potential interaction using AlphaFold3. This analysis suggested a possible interaction between lnc243 and beta-catenin, which was further supported by RNA immunoprecipitation showing that beta-catenin binds to lnc243. Moreover, knockdown of lnc243 led to a decrease in the post-translational levels of beta-catenin. Mutations in Wnt pathway genes are rare in PDAC; however, increased lnc243 expression may represent an alternative mechanism for dysregulating beta-catenin and promoting malignancy in PDAC.