Long noncoding RNA LINC00152 is a potential prognostic biomarker in patients with high-grade glioma

CNS Neurosci Ther. 2018 Oct;24(10):957-966. doi: 10.1111/cns.12850. Epub 2018 Mar 25.

Abstract

Aims: To investigate the role of LINC00152 in high-grade glioma (HGG).

Methods: We collected data from the Chinese Glioma Genome Atlas (CGGA) microarray, CGGA RNA sequencing, and GSE16011 datasets to evaluate the expression and prognostic relationship of LINC00152 in patients with HGGs. A knockdown assay was performed to determine the function of LINC00152 in glioma development and progression in vitro and in vivo.

Results: The expression of LINC00152 was increased with glioma grade, especially in the mesenchymal TCGA subtype. LINC00152 was independently associated with poor prognosis, and the overall survival (OS) of the high expression group was shorter than the low expression group (median OS 14.77 vs 9.65 months; P = 0.0216) in the CGGA microarray dataset. The results were validated in the other 2 datasets. Based on the expression of LINC00152, 4288 (2519 positively; 1769 negatively) probes were extracted to perform a biological process analysis using the Database for Annotation, Visualization, and Integrated Discovery. Positively regulated genes were enriched in immune response, apoptotic process, cell adhesion, and regulation of cell proliferation. The clinical and molecular features of HGG patients indicated that patients in the LINC00152 high expression group tended to display the mesenchymal type, older (≥46 years), isocitrate dehydrogenase1 wild-type, O(6)-methylguanine DNA methyltransferase unmethylated, nonchemotherapy, and low karnofsky performance status. Functionally, knockdown of LINC00152 inhibited cell proliferation, migration, and invasion and increased the sensitivity of chemotherapy in vitro.

Conclusion: Our results indicate that knockdown of LINC00152 could inhibit tumor growth in vivo. LINC00152 could serve as a potential prognostic biomarker in patients with HGG.

Keywords: LINC00152; RNA sequencing; glioma; long noncoding RNA; microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioma / diagnosis
  • Glioma / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice, Nude
  • Microarray Analysis
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Transduction, Genetic
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Long Noncoding
  • RNA, Small Interfering
  • long non-coding RNA Linc00152, human