ALG2 regulates glioblastoma cell proliferation, migration and tumorigenicity

Biochem Biophys Res Commun. 2017 Apr 29;486(2):300-306. doi: 10.1016/j.bbrc.2017.03.032. Epub 2017 Mar 12.

Abstract

Apoptosis-linked gene-2 (ALG-2), also known as programmed cell death 6 (PDCD6), has recently been reported to be aberrantly expressed in various tumors and required for tumor cell viability. The aim of the present study was to investigate whether ALG-2 plays a crucial role in tumor cell proliferation, migration and tumorigenicity. In this study, we examined the expression of PDCD6 in glioblastoma cell lines and found that ALG-2 was generally expressed in glioblastoma cell lines. We also performed an analysis of an online database and found that high expression of ALG-2 was associated with poor prognosis (p = 0.039). We found that over-expression of ALG2 in glioblastoma could inhibit cell proliferation and, conversely, that down-regulation of ALG2 could promote cell proliferation. Further studies showed that over-expression of ALG2 inhibited the migration of tumor cells, whereas down-regulation of ALG2 promoted tumor cell migration. Finally, in vitro and in vivo studies showed that over-expression of ALG2 inhibited the tumorigenic ability of tumor cells, while down-regulation of ALG2 promoted tumor cell tumorigenic ability. In conclusion, ALG2 has a tumor suppressive role in glioblastoma and might be a potential target for the treatment of glioblastoma.

Keywords: ALG-2; Glioblastoma; Migration; PDCD6; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Calcium-Binding Proteins / antagonists & inhibitors
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Databases, Factual
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Survival Analysis

Substances

  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Oligonucleotides
  • PDCD6 protein, human