LIN28 is involved in glioma carcinogenesis and predicts outcomes of glioblastoma multiforme patients

PLoS One. 2014 Jan 24;9(1):e86446. doi: 10.1371/journal.pone.0086446. eCollection 2014.

Abstract

LIN28, an evolutionarily conversed RNA binding protein which can bind to the terminal loops of let-7 family microRNA precursors and block their processing to maturation, is highly expressed in several subsets of tumors that carry poor prognoses, such as ovarian carcinoma, hepatocellular carcinoma, colon carcinoma and germ cell carcinoma. However, there has been no study on the expression of LIN28 in glioma tissues or their importance as a prognostic predictor of glioma patients. This study aimed to examine the expression of LIN28 in glioma and correlate the results to patient outcome. We found that LIN28 expression was significantly higher in the group of patients with a poor prognosis compared to patients with a good prognosis by gene microarray. Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level. Similar results were also obtained from the tissue microarray analysis. Univariate and multivariate analyses showed high LIN28 expression was an independent prognostic factor for a shorter progression-free survival and overall survival in GBM patients. Furthermore in vitro experiments showed that down-regulation of LIN28 in U251 and U373 cells caused cell cycle arrest in the G1 phase, delayed cell proliferation, increased apoptosis, and resulted in fewer colonies compared to controls. Summarily, our data provides a potential target for cancer therapy as an approach to overcome the poor options currently available for GBM patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / diagnosis
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Survival Analysis
  • Tissue Array Analysis

Substances

  • Lin28A protein, human
  • RNA, Small Interfering
  • RNA-Binding Proteins

Grants and funding

This work was supported by National Nature Science Foundation of China (NO. 81272781, 81201535), Program for academic leaders in health sciences (No. XBR2011030) and “Shu Guang” project (No.11SG37) in Shanghai, Nature Science Foundation of Shanghai (12ZR1436000) and the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2012KIP203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.