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Tumor Biology

, Volume 36, Issue 6, pp 4189–4196 | Cite as

Downregulation of Id2 increases chemosensitivity of glioma

Research Article

Abstract

With its growth characteristic and chemoresistance, glioblastoma is the most deadly brain tumor. Twenty-five core genes that influence the chemosensitivity of glioblastoma were screened in our previous experiments, and Id2, the inhibitor of DNA binding 2, an oncogene encoding a helix–loop–helix protein, was identified. The elevated expression levels of Id2 have been reported in several malignancies. The aim of this study is to investigate the effects of Id2 expression on the chemosensitivity of glioma cells. In this study, Id2 expression was investigated in a malignant glioma cell line. Then, we silenced the expression of Id2 with the highly specific posttranscriptional suppression of RNA interference (RNAi) in U87 cells. The changes in response to antitumor agents Me-CCNU, VM26, and TMZ were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured using an annexin V–fluorescein isothiocyanate (FITC) apoptosis detection kit. The relationship between Id2 expression and caspase 3 was tested by RT-PCR and Western blot. This study demonstrated that Id2 was significantly upregulated in glioma tissues, and Id2 correlated well with the advancement of glioma grade and a worse prognosis in response to temozolomide treatment. The RNAi-mediated decrease of Id2 expression enhanced chemosensitivity to Me-CCNU, VM26, and TMZ in the U87 cell line. We further discovered that silencing of Id2 expression could promote apoptosis of glioblastoma cells, which could be attributed to the fact that Id2 affects tumor cell chemosensitivity. Downregulation of the Id2 gene by RNAi could increase the chemosensitivity of glioblastoma cells. Id2 could be a good molecular target for glioblastoma gene therapy.

Keywords

Id2 Glioblastoma Chemosensitivity RNA interference 

Abbreviations

Id2

Inhibitor of DNA binding 2, dominant negative helix–loop–helix protein

GBM

Glioblastoma

RNAi

RNA interference

siRNA

Small interfering RNA

Me-CCNU, methyl-CCNU

Semustine

VM26

Teniposide

TMZ

Temozolomide

RT-PCR

Reverse transcription-polymerase chain reaction

HAc

Human astrocytes-cerebellar

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81302187 and No. 30930094) and medical technological innovation funding of Nanjing Military Region in 2014 (No. ZD15).

Conflict of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of NeurosurgeryChinese PLA General HospitalBeijingChina
  2. 2.Department of Neurosurgery, Changzheng HospitalSecond Military Medical UniversityShanghaiChina
  3. 3.Department of RadiologyThe 105th Hospital of PLAHefeiChina
  4. 4.Department of Radiology, Xiang Ya HospitalCentral South UniversityChangshaChina
  5. 5.CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhouChina
  6. 6.Department of NeurosurgeryChinese PLA General HospitalBeijingChina
  7. 7.Department of NeurosurgeryThe 163th Hospital of Chinese PLA (Second Affiliated Hospital of Hunan Normal University)ChangshaChina

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