Long non-coding RNA LINC01018 inhibits human glioma cell proliferation and metastasis by directly targeting miRNA-182-5p

J Neurooncol. 2022 Oct;160(1):67-78. doi: 10.1007/s11060-022-04113-5. Epub 2022 Sep 12.

Abstract

Aim: Accumulating evidence suggests that lncRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise function of most lncRNAs in glioma remains unknown. In this study, we explored the role of long intergenic non-protein coding RNA 1018 (LINC01018) in human glioma.

Methods: Expression levels of LINC01018 and miR-182-5p in clinical glioma tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). Cell proliferation, migration, and invasion were determined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Epithelial-mesenchymal transition (EMT) related proteins were measured by Western blotting. Direct relationship between LINC01018 and miR-182-5p was tested by dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and rescue assays. Lastly, bioinformatics analyses were conducted to predict the downstream factors of LINC01018/miR-182-5p axis in glioma.

Results: LINC01018 was significantly down-regulated in glioma tissues and cell lines. Overexpression of LINC01018 dramatically inhibited cell proliferation, migration, and invasion and reverse EMT process in glioma. LINC01018 directly target to miR-182-5p. Forced up-regulation of miR-182-5p reversed the inhibitory effects on proliferative and metastatic abilities of glioma cells with LINC01018 overexpression. Lastly, the bioinformatics analyses revealed that LINC01018/miR-182-5p axis mediated a cluster of downstream genes (ADRA2C, RAB6B, RAB27B, RAPGEF5, STEAP2, TAGLN3, and UNC13C), which were potential key factors in the development of glioma.

Conclusion: LINC01018 inhibits cell proliferation and metastasis in human glioma by targeting miR-182-5p, and should be considered as a potential therapeutic target in this cancer.

Keywords: Glioma; LINC01018; Long noncoding RNAs; Tumor-suppressor gene; miR-182-5p.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioma* / genetics
  • Glioma* / pathology
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • Mirn182 microRNA, human