Expression of circular RNA CDR1-AS in colon cancer cells increases cell surface PD-L1 protein levels

The expression of CDR1-AS, a representative circular RNA, is closely linked with poor prognosis in gastrointestinal cancers, such as colon, liver, and pancreatic cancers. Although it is well known that CDR1-AS antagonizes microRNA-7 function through its sequence similarities in the brain, its biological function and link with the malignant potential of cancer cells remain unclear, partly due to the difficulties of ectopic expression of circular RNAs. In the present study, SW620, a colon cancer cell line that stably expresses CDR1-AS RNA circularized, was established using the laccase 2 gene cassette, and its biological function associated with malignant behavior was determined. In contrast to previous studies, cell growth or invasion ability was not altered by CDR1-AS expression. However, the expression levels of CMTM4 and CMTM6, which were recently recognized as critical regulators of PD-L1 protein expression at the cell surface, were significantly increased. Accordingly, the cell surface PD-L1 protein levels were increased in CDR1-AS-expressing cells. Notably, the effects were not canceled out by overexpressing microRNA-7, indicating that the increase in cell surface PD-L1 in CDR1-AS-expressing cells was not dependent on microRNA-7 function. These results indicated that expression of this circular RNA in cancer cells may lead to poor prognosis by increasing cell surface PD-L1 levels through microRNA-7-independent mechanisms.