Polymerase I and transcript release factor acts as an essential modulator of glioblastoma chemoresistance

Xin Wang; Tianzhu Liu; Yifeng Bai; Hongzhan Liao; Shengcong Qiu; Zhenhua Chang; Yanting Liu; Xiaohui Yan; Hongbo Guo

doi:10.1371/journal.pone.0093439

Polymerase I and transcript release factor acts as an essential modulator of glioblastoma chemoresistance

PLoS One. 2014 Apr 18;9(4):e93439. doi: 10.1371/journal.pone.0093439. eCollection 2014.

Authors

Xin Wang¹, Tianzhu Liu², Yifeng Bai³, Hongzhan Liao², Shengcong Qiu², Zhenhua Chang⁴, Yanting Liu², Xiaohui Yan⁵, Hongbo Guo²

Affiliations

¹ The National Key Clinic Specialty, the Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, P. R. China; Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P. R. China.
² The National Key Clinic Specialty, the Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, P. R. China.
³ Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, P. R. China.
⁴ Department of Laboratory Medicine, Tongchuan People's Hospital, Tongchuan, P. R. China.
⁵ Clinical Research Centre, Nanfang Hospital of Southern Medical University, Guangzhou, P. R. China.

Abstract

Objectives: This study is to investigate if polymerase I and transcript release factor (PTRF) acts as a modulator in glioblastoma (GBM) chemoresistance.

Methods: Multidrug resistant (MDR) GBM cell line U251AR was established by exposing the U251 cell line to imatinib. The 2D-DIGE and MALDI-TOF/TOF-MS were performed on U251 and U251AR cell lines to screen MDR-related proteins. The expression of PTRF was determined by Western blot and quantitative RT-PCR analyses.

Results: When compared with the parental U251 cells, expression of 21 proteins was significantly altered in U251AR cells. Among the 21 differentially expressed proteins, the expression of PTRF was up-regulated by 2.14 folds in U251AR cells when compared with that in the parental U251 cells. Knockdown of PTRF in GBM cell lines significantly increased chemosensitivity of cells to various chemical drugs and decreased the expression levels of caveolin1, a major structural component of caveolae. Expression levels of PTRF and caveolin1 were significantly up-regulated in the relapsed GBM patients. The mRNA level of PTRF and caveolin1 showed a positive correlation in the same GBM specimens.

Conclusions: Our results indicate that PTRF acts as a modulator in GBM chemoresistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzamides / pharmacology
Caveolin 1 / metabolism
Cell Line, Tumor
Drug Resistance, Neoplasm*
Gene Expression Regulation, Neoplastic / drug effects
Gene Knockdown Techniques
Glioblastoma / drug therapy
Glioblastoma / metabolism*
Glioblastoma / pathology
Humans
Imatinib Mesylate
Piperazines / pharmacology
Proteomics
Pyrimidines / pharmacology
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Recurrence

Substances

Benzamides
CAVIN1 protein, human
Caveolin 1
Piperazines
Pyrimidines
RNA-Binding Proteins
Imatinib Mesylate

Grants and funding

This work was supported by National Nature Science Foundation of China (81041068, 30971183, 81372691), the Funds for Key Sci-Tech Research Projects of Guangdong (2009B030801230), Nature Science Foundation of Guangdong Province, China (S2011010004065). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.