Circ_0091579 Serves as a Tumor-Promoting Factor in Hepatocellular Carcinoma Through miR-1225-5p/PLCB1 Axis

Dig Dis Sci. 2022 Feb;67(2):585-597. doi: 10.1007/s10620-021-06861-2. Epub 2021 Feb 8.

Abstract

Background: Hepatocellular carcinoma (HCC) is a dreadful threaten to human health worldwide. Many circular RNAs were reported to influence the malignant development of HCC. The aim of this study was to elucidate the role of circ_0091579 in HCC progression and the molecular fundamentation.

Methods: Expression of circ_0091579, microRNA-1225-5p (miR-1225-5p), and phospholipase C, β1 (PLCB1) was examined by quantitative reverse transcription-polymerase chain reaction or Western blotting. Cell viability, clonogenicity capacity, and apoptosis were determined via Cell Counting Kit-8 assay, colony formation assay, and flow cytometry, respectively. Transwell assay was employed to detect cell migration and invasion. Target relationship between miR-1225-5p and circ_0091579 or PLCB1 was demonstrated by dual-luciferase reporter assay. Moreover, role of circ_0091579 in vivo was assessed by Xenograft model assay.

Results: Expression of circ_0091579 and PLCB1 was increased, while miR-1225-5p expression was decreased in HCC tissues and cells. Circ_0091579 or PLCB1 depletion had inhibitory effects on HCC cell proliferation and metastasis. Circ_0091579 sponged miR-1225-5p to upregulate PLCB1 expression in HCC cells. Silencing of miR-1225-5p contributed to HCC progression, which was mitigated by PLCB1 depletion. Circ_0091579 deficiency could suppress HCC tumor growth in vivo.

Conclusion: Circ_0091579 knockdown repressed HCC progression and tumorigenesis by regulating miR-1225-5p/PLCB1 axis, affording a novel molecular basis for HCC development.

Keywords: Circ_0091579; Hepatocellular carcinoma; PLCB1; miR-1225-5p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Gene Knockdown Techniques
  • Glypicans / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • Phospholipase C beta / genetics*
  • Phospholipase C beta / metabolism
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • GPC3 protein, human
  • Glypicans
  • MIRN1225 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • PLCB1 protein, human
  • Phospholipase C beta