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

J Clin Lab Anal. 2020 Apr;34(4):e23138. doi: 10.1002/jcla.23138. Epub 2019 Dec 27.

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 (IC50 ) 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.

Keywords: cell proliferation; chemotherapy sensitivity; circular RNA SMARCA5; intrahepatic cholangiocarcinoma; prognosis.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Factor Analysis, Statistical
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Up-Regulation / genetics

Substances

  • RNA, Circular
  • Deoxycytidine
  • Cisplatin
  • Gemcitabine