Colorectal cancer (CRC) is among the leading causes of cancer-related mortality worldwide. Compelling evidence suggests that long non-coding RNA (lncRNAs) can control carcinogenesis by regulating various aspects of cell biology. However, limited number of CRC-related lncRNAs has been well characterized. This study was undertaken to investigate the expression pattern of the novel lncRNA-CCHE1 in CRC patients and to examine its correlation with clinicopathological features, ERK/COX-2 pathway and some cell proliferation markers in order to gain biological insights on its role in CRC pathogenesis. Colon cancer specimens with their adjacent non-cancerous tissues were taken from 60 patients with primary CRC. LncRNA-CCHE1 relative expression was assessed using quantitative real-time RT-PCR. P-ERK ½ and cyclin D1 levels were estimated by ELISA. COX-2 and proliferating cell nuclear antigen (PCNA) expression were assessed immunohistochemically. lncRNA-CCHE1 expression was upregulated in CRC tissues compared to adjacent non-cancerous tissues, and was significantly associated with larger tumor size, less differentiated histology, advanced dukes' stage, positive lymph node involvement and vascular invasion. It also showed a significant positive correlation with the expression of p-ERK1/2, COX-2 as well as cyclin D1and PCNA (as markers for cell proliferation). These findings signify that lncRNA-CCHE1 is a key oncogene possibly involved in CRC development and progression by modulating ERK/COX-2 pathway and cell proliferation activity. Our study also provides a rationale for potential use of lncRNA-CCHE1 as a novel prognostic marker, and opens the door for the development of lncRNA-CCHE1-directed therapeutic approaches for CRC patients.
Keywords: COX-2; Colorectal carcinoma; Cyclin D1; ERK1/2; Long non-coding RNA CCHE1; PCNA.