Circular RNA SMARCA5 correlates with favorable clinical tumor features and prognosis, and increases chemotherapy sensitivity in intrahepatic cholangiocarcinoma.

OBJECTIVE: This present study aimed to investigate the correlation of circular RNA SMARCA5 (circ-SMARCA5) with clinicopathological features and overall survival (OS), and the effect of circ-SMARCA5 on cell proliferation and chemotherapy sensitivity to cisplatin/gemcitabine in intrahepatic cholangiocarcinoma (ICC). METHODS: Totally 92 primary ICC patients who underwent resection were recruited, and their tumor tissues and adjacent tissues were collected for circ-SMARCA5 detection. The effect of circ-SMARCA5 on cell proliferation and chemotherapy sensitivity was detected after circ-SMARCA5 overexpression plasmid transfection into TFK-1 and HuH-28 ICC cells. RESULTS: Circ-SMARCA5 expression was reduced in ICC tumor tissues compared to adjacent tissues. Tumor circ-SMARCA5 high expression was negatively associated with Eastern Cooperative Oncology Group performance score, T stage, N stage, TNM stage, and abnormal CA199 status. Furthermore, OS was increased in patients with tumor circ-SMARCA5 high expression compared with those with low expression, and further multivariate Cox's regression demonstrated that tumor circ-SMARCA5 high expression was an independent predictive factor for longer OS. In TFK-1 and HuH-28 ICC cells, circ-SMARCA5 upregulation decreased cell proliferation, reduced relative cell viability in cisplatin-treated as well as gemcitabine-treated cells, and also decreased inhibitory concentration by 50% value (IC(50) ) of cisplatin and gemcitabine. CONCLUSION: The correlation of circ-SMARCA5 with favorable clinical tumor features, survival profile, and its promoting effect on chemotherapy sensitivity implies its potential as a valuable biomarker in monitoring disease progression and prognosis of ICC.