OCC-1D regulates Wnt signaling pathway: potential role of long noncoding RNA in colorectal cancer.

Aberrant activation of the Wnt signaling pathway is observed in most colorectal cancers (CRC). OCC-1D is a splice variant of OCC-1 gene which is considered as a long noncoding RNA (lncRNA) due to lacking the translational initiation codon of the gene. Here, we sought supporting evidence for the effects of OCC-1D on the Wnt pathway and cell cycle progression in CRC. TOP/FOPflash assay and qRT-PCR indicated that expression alterations of OCC-1D could change Wnt signaling activity in colon cancer cells. Consistently, immunocytochemistry results showed the effect of OCC-1D overexpression on nuclear localization of β-catenin proteins in SW480 cells. Flow cytometry, wound healing and MTT assay confirmed the cell cycle stimulatory effects of OCC-1D in CRC-originated cell lines (SW480 and HCT116). qRT-PCR revealed a positive correlation between the expression level of OCC-1D and its neighboring gene, APPL2. Two distinct tests, downregulation of APPL2 mRNA by using shRNA and Wnt signaling inhibition by using small molecule, along with OCC-1D overexpression confirmed that OCC-1D lncRNA exerts its effect on Wnt signaling pathway through expression modulation of APPL2 gene. Collectively, we suggested the putative regulatory effects of OCC-1D lncRNA on cell cycle progression and Wnt signaling activation through enhancing the APPL2 gene transcription.