RNA sequencing reveals differential expression of circular RNAs in human small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive malignancy with a poor prognosis. SCLC tumors are classified into four molecular subtypes each exhibiting distinct biological traits and therapeutic vulnerabilities. However, limited information is available on the expression profile of circular RNAs (circRNAs) in SCLC. To address this gap, we performed RNA sequencing to identify differentially expressed circRNAs (DECs) in SCLC compared with normal lung tissue. Using CircInteractome and miRTarBase, we predicted miRNA partners and their downstream mRNA targets, thereby constructing circRNA–miRNA–mRNA regulatory networks. The expression of circRNAs and a few predicted interacting miRNAs in SCLC and normal lung tissue was validated using qRT-PCR, and their diagnostic performance was assessed. Among the identified 23 DECs, 10 were significantly downregulated and 13 were upregulated in SCLC. In total, 241 miRNAs were predicted to interact with these 23 DECs, potentially regulating 7,804 mRNA targets. Further validation revealed significant downregulation of circLIFR expression and overexpression of circCAMSAP1 in SCLC. The circLIFR-associated network comprised 26 miRNAs and 2,447 mRNA targets, with miR-1234-3p and miR-375-3p significantly upregulated in SCLC. The circCAMSAP1-associated network included 14 miRNAs and 553 mRNA targets, with miR-145-5p significantly downregulated in SCLC. Interestingly, the expression of circCAMSAP1 significantly correlated with the response to therapy. As diagnostic biomarkers, circLIFR and circCAMSAP1 exhibited the AUC of 0.9177 and 0.764, respectively. In conclusion, certain DECs may regulate key hallmarks of SCLC through miRNA sponging. These findings highlight circLIFR and circCAMSAP1 as promising biomarkers, though functional validation is required to confirm their mechanistic roles.