Long non‑coding RNA LINC00238 suppresses the malignant phenotype of liver cancer by sponging miR‑522

Mol Med Rep. 2022 Feb;25(2):71. doi: 10.3892/mmr.2022.12587. Epub 2022 Jan 11.

Abstract

Long non‑coding RNAs can regulate the malignant tumor phenotype either as tumor suppressors or oncogenes. The present study investigated the underlying mechanism of LINC00238 in liver cancer. LINC00238 was identified as a downregulated molecule in The Cancer Genome Atlas liver hepatocellular carcinoma dataset through Gene Expression Profiling Interactive Analysis software. Through gain‑ and loss‑of‑function experiments, LINC00238 was confirmed as a tumor suppressor that could not only decrease cell viability, migration and invasion in vitro, but also tumorigenesis and tumor metastasis in vivo. By cytoplasmic and nuclear RNA isolation, LINC00238 was confirmed to be predominantly cytoplasmic. Mechanistically, RNA pull‑down assays showed that LINC00238 sponged microRNA (miR)‑522 and then reversed the inhibitory effects on two downstream targets, secreted frizzled related protein 2 and dickkopf1. Collectively, LINC00238 was identified as a tumor suppressor that acts via sponging miR‑522 followed by silencing of downstream targets, suggesting that LINC00238 may have a key role in suppressing the malignant phenotype of liver cancer cells.

Keywords: DKK1; LINC00238; SFRP2; liver cancer; lncRNA; miR‑522.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Chickens
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Biological
  • Phenotype
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*

Substances

  • MIRN522 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

Funding: No funding was received.