Integrated dysregulation of RNF43 and associated lncRNAs reveals transcriptional remodeling in colorectal carcinoma

Abstract

The Wnt signaling cascade is crucial for diverse biological processes, including cell cycle regulation, inflammation, embryonic development, and tumorigenesis. The present study investigates the expression of TSPOAP1-AS1, TMEM147-AS1, and FOXP4-AS1 lncRNAs, along with RNF43, all of which are associated with the Wnt/β-catenin signaling pathway, in colorectal cancer (CRC) samples compared to adjacent normal tissues (ANTs). RNF43 was significantly overexpressed in CRC samples, with a median 2.34-fold increase relative to normal tissues (P value = 0.04). In contrast, the lncRNA TSPOAP1-AS1 was markedly down-regulated in tumors, showing a median 0.42-fold reduction (P value = 0.03). The remaining two lncRNAs—TMEM147-AS1 and FOXP4-AS1—were also significantly elevated, exhibiting median fold-changes of 2.94-fold (P value < 0.0001) and 2.02-fold (P value = 0.003), respectively. All four transcripts achieved exceptionally high specificity (97.5–100 %) but only moderate sensitivity (29.3–56.1 %) for discrimination of CRC samples from ANTS, reflecting their stringent discrimination of ANTs at the expense of missing a subset of tumors. Taken together, our results revealed a coordinated dysregulation of Wnt-related genes in CRC, i.e. loss of TSPOAP1-AS1 alongside gain of RNF43, TMEM147-AS1, and FOXP4-AS1 expression, highlighting their potential as complementary biomarkers.