Circular RNA Circ100084 functions as sponge of miR‑23a‑5p to regulate IGF2 expression in hepatocellular carcinoma

Mol Med Rep. 2020 Jun;21(6):2395-2404. doi: 10.3892/mmr.2020.11069. Epub 2020 Apr 10.

Abstract

Hepatocellular carcinoma (HCC) has become a major cause of cancer‑related mortality worldwide. Circular RNAs (circRNAs) are non‑coding RNAs that serve important roles in multiple cancers. However, the role of circRNAs in HCC remains largely unknown. In the present study, a circRNA microarray dataset of HCC samples, GSE97332, was downloaded from the gene expression omnibus database. Following data preprocessing, differentially expressed circRNAs between HCC tissues and normal tissues were determined using GEO2R. The circRNA‑miRNA interactions were predicted by the miRanda database. The miRTarbase database was used to search for target genes of the miRNAs. A circRNA‑miRNA‑mRNA network was constructed using Cytoscape based on the obtained circRNA, miRNA and mRNA. In this network, the upregulated circRNA hsa_circRNA_100084 was found to be involved in a competing endogenous relationship of hsa_circRNA_100084‑hsa‑miR‑23a‑5p‑ insulin‑like growth factor 2 (IGF2). The differential expression of hsa_circRNA_100084, hsa‑miR‑23a‑5p and IGF2 in HCC tissues and liver cancer cells was validated by reverse transcription‑quantitative PCR. Additionally, the interactions between hsa‑miR‑23a‑5p with hsa_circRNA_100084 and IGF2 were validated by dual‑luciferase reporter assays. Knocking down hsa_circRNA_100084 inhibited the proliferation, migration and invasion of liver cancer cells, while the simultaneous overexpression of IGF2 reversed the effects of hsa_circRNA_100084 knockdown. The results show that hsa_circRNA_100084 could promote the expression of IGF2 by acting as a sponge of hsa‑miR‑23a‑5p in liver cancer cells.

Keywords: hepatocellular carcinoma; circular rna; mirna; sponge.

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Insulin-Like Growth Factor II / chemistry
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA Interference
  • RNA, Circular / antagonists & inhibitors
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Small Interfering / metabolism
  • Sequence Alignment

Substances

  • 3' Untranslated Regions
  • IGF2 protein, human
  • MIRN23a microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering
  • Insulin-Like Growth Factor II