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

Abstract

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. K E Y W O R D Scell proliferation, chemotherapy sensitivity, circular RNA SMARCA5, intrahepatic cholangiocarcinoma, prognosis

Regulation of circGOLPH3 and its binding protein CBX7 on the proliferation and apoptosis of prostate cancer cells

“…Additionally, over-expression of miR-181b/d promotes PC-3 cell proliferation[8]. circ-SMARCA5 is an oncogene for prostate cancer, which promotes cell cycle and inhibits apoptosis[9].Unlike linear RNA, the structure of circRNA is a covalently closed loop with no tail at the 5'-3' port. This structure is endowed with the resistance against digestion of RNase that keeps itself intact.…”

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

“…Hepatocellular carcinoma Circ_0003418 and circRNA_ 101505 are decreased in HCC tissues, while circ-SMARCA5 is reduced in intrahepatic cholangiocarcinoma (ICC) [31,160,161]. Silencing circ_0003418 promotes cisplatin resistance, probably though miR-7-and miR-383mediated effects on the Wnt/β-catenin pathway, but this mechanism still needs further investigation [161].…”

“…Cir-cRNA_101505 is especially lower in cisplatin-resistant HCC cells than in sensitive cells [31]. HCC or ICC patients with a lower level of circRNA_101505 or circ-SMARCA5 have a shorter overall survival period than patients with higher levels of these circRNAs [31,160]. Overexpression of circRNA_101505 increases its ability to sponge miR-103 and subsequently elevates the expression of the tumor suppressor oxidored-nitro domaincontaining protein 1 (NOR1), which sensitizes HCC cells to cisplatin-induced apoptosis [31].…”

“…Overexpression of circRNA_101505 increases its ability to sponge miR-103 and subsequently elevates the expression of the tumor suppressor oxidored-nitro domaincontaining protein 1 (NOR1), which sensitizes HCC cells to cisplatin-induced apoptosis [31]. The upregulation of circ-SMARCA5 could enhance the sensitivity of ICC cells to cisplatin and gemcitabine [160].…”

CircRNAs: biogenesis, functions, and role in drug-resistant Tumours

“…Overexpression of circCRIM1 promotes NPC cell metastasis and EMT. CircCRIM1 can competitively bind miR-422a and block the inhibitory effect of miR-422a on its target gene FOXQ1, resulting in metastasis, EMT, and DTX resistance in NPC [ 154 ]. Additionally, upregulation of circCRIM1 is associated with poor survival of NPC patients.…”