Role and mechanism of circ-PRKCI in hepatocellular carcinoma

World J Gastroenterol. 2019 Apr 28;25(16):1964-1974. doi: 10.3748/wjg.v25.i16.1964.

Abstract

Background: The circular RNA circ-PRKCI is an endogenous non-coding RNA that forms a covalently closed ring after reverse splicing, which plays a key role in the occurrence and development of multiple digestive system tumors.

Aim: To investigate the role and mechanism of circ-PRKCI in the occurrence and development of hepatocellular carcinoma (HCC).

Methods: This study used real-time polymerase chain reaction to detect the expression of circ-PRKCI in tumor tissues, tumor adjacent tissues, and blood in patients with HCC and other digestive system tumor cells. A series of functional tests were performed to explore whether circ-PRKCI affects the growth of HCC cells and what is its mechanism in HCC. Meanwhile, fluorescence in situ hybridization was used to detect the subcellular localization of circ-PRKCI. Survival analysis was performed to predict the correlation between circ-PRKCI and the prognosis of HCC. Chi-square test and t-test were performed for statistical analyses.

Results: The level of circ-PRKCI was significantly higher in HCC tissues than in tumor adjacent tissues, and in HCC cell lines than in cells lines of esophageal, liver, stomach, and colon cancers. A series of functional tests showed that circ-PRKCI substantially inhibited cell apoptosis and promoted cell invasion. It was found that circ-PRKCI can act as the sponge of miRNA-545 to reduce the expression of AKT3 protein. Moreover, the result of survival analysis showed that circ-PRKCI target gene E2F7 can reduce liver cancer patients' survival rate. And clinical data suggested that the distribution of circ-PRKCI rose with the depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, indicating that circ-PRKCI may affect the survival and prognosis of patients with HCC by regulating E2E7.

Conclusion: This study explores the role and mechanism of circ-PRKCI in HCC, which provides a new research direction and theoretical basis for the treatment of HCC.

Keywords: Cell invasion; Circ-PRKCI; Hepatocellular carcinoma; Progression; Protein kinase B signaling pathway.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • E2F7 Transcription Factor / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liver / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Prognosis
  • RNA, Circular / metabolism*
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • E2F7 Transcription Factor
  • E2F7 protein, human
  • RNA, Circular