The pathogenesis of liver cancer has not been fully elucidated yet. Bile acids are components of bile, which are inorganic substances and regulate tumor progression. However, the differential expression profile of liver cancer cell proteins after bile acid treatment remains unclear. Human hepatoma cell line SMMC7721 was cultured and randomly assigned into control group and bile acid group followed by measuring the protein expression profile by protein fingerprinting. SMMC7721 cells were transfected with UGT2B or UGT2B, followed by analysis of UGT2B expression, cell proliferation, apoptosis, migration and PI3K/AKT signaling protein expression. The most obvious proteins with an increased expression after bile acid treatment were UGT2B, AAP, APLP2, LAPTM4B, NCOA4 with UGT2B being the most significant one. Overexpression of UGT2B decreased cell proliferation, promoted cell apoptosis, downregulated migration ability and AKT phosphorylation (P <0.05). UGT2B siRNA transfection significantly down-regulated UGT2B expression, promoted cell proliferation, decreased apoptosis rate, increased migration ability and AKT phosphorylation (P <0.05). In conclusion, bile acid can alter the protein expressions of liver cancer cells, with UGT2B being changed most obviously. UGT2B can affect liver cancer cell behaviors via modulating PI3K/AKT signaling.
Background 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, 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 plasmids 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 (IC50) of cisplatin and gemcitabine.Conclusions The correlation of circ-SMARCA5 with favorable clinical tumor features, survival profile, and its promoting effect on chemotherapy sensitivity imply its potential as a valuable biomarker in monitoring disease progression and prognosis of ICC.
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