The role of miR-21, miR-223, and CLDN8 detection in UC-associated colorectal cancer

Abstract

Abstract Background Ulcerative colitis (UC) is an inflammatory bowel disease that leads to UC-associated colorectal cancer (UC-CRC), causing high mortality. Understanding UC-CRC's molecular mechanisms is vital for early diagnosis and treatment. The sensitivity and specificity of traditional tumor markers such as CEA, CA199, and CA153 are poor, establishing the need for more sensitive detection markers. Here we describe the clinical application of miR-21 and miR-223 combined with CLDN8 as new UC-CRC biomarkers. Methods The expression of CLDN8, miR-21, and miR-223 were detected by immunohistochemistry and Q-PCR. The diagnostic values of miRNAs and CLDN8 were evaluated using receiver operating characteristic curves and the area under the curve. The optimal specificity and sensitivity were according to the Youden index, (Youden index = Sensitivity + Specificity − 1). The diagnostic panels were constructed using a stepwise logistic regression model. Cell proliferation and apoptosis were measured by the CCK-8 assay and flow cytometry. Results CLDN8 was downregulated in the tissues of UC-CRC, and the expression of miR-21 and miR-223 both in the serum and intestinal mucosa tissues of patients with UC-CRC was higher compared with that of the control group. miR-21 and miR-223 combined with CLDN8 as a molecular marker of UC-related CRC are superior to traditional tumor markers. Corresponding changes occurred in downstream signaling pathway proteins related to CLDN8 and epithelial-to-mesenchymal transition (EMT) after miR-21 and miR-223 transfection. Conclusion miR-21 and miR-223 can destroy tight junctions between intestinal epithelial cells by targeting CLDN8 and promoting the occurrence and development of UC-CRC through EMT. Therefore, the combination of serum miR-21 and miR-223 and tissue CLDN8 detection is expected to become a new biomarker for early diagnosis and prognostic monitoring of UC-CRC.