Format

Send to

Choose Destination
Aging (Albany NY). 2018 May 10;10(5):988-999. doi: 10.18632/aging.101442.

A novel functional polymorphism of GFAP decrease glioblastoma susceptibility through inhibiting the binding of miR-139.

Author information

1
Department of Neurosurgery, The Shanghai Neuromedical Center, Qingdao University, Shanghai, China.
2
Department of Neurosurgery, PuTuo District People's Hospital, Shanghai, China.
3
Department of pathology, People's Hospital of Rizhao, Rizhao, Shandong, China.
4
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
5
Department of Cardiovascular Surgery of the First Affiliated Hospital& Institute for Cardiovascular Science, Soochow University, Suzhou, Jiangsu, China.
#
Contributed equally

Abstract

Glioblastoma (GBM) is the most commonly diagnosed solid tumor outside the central nervous system. However, genetic factors underlying GBM remain largely unclear. Previous studies indicated that Glial fibrillary acidic protein (GFAP) might play an important role in the aggressiveness of GBM and also contributed to its poor overall survival. The present study aims to test (1) the associations between GFAP single nucleotide polymorphisms (SNPs) and GBM cells chemoresistance and metastasis, and (2) the molecular mechanism accounting for their effects. Four tagging SNPs of GFAP were initially genotyped in 667 subjects and the significant SNP was further analyzed via online bioinformatical tools. SNP rs11558961 was found to be significantly associated with GBM susceptibility. It was predicted to influence microRNA(miR)-139 binding to 3'UTR of GFAP gene. In functional experiments, we found that cells transfected with rs11558961 G-allele constructs had lower baseline luciferase activities and were more responsive to miR-139 changes, compared to C-allele constructs. Moreover, rs11558961 C>G variant reduced the chemoresistance of GBM cells and migration capability. In conclusion, rs11558961 might influence the chemoresistance and progression of GBM cells via promoting the binding of miR-139, ultimately decrease the susceptibility of GBM. This investigation will shed light on the optimizing for clinical trial design and individualizing of therapeutic plans.

KEYWORDS:

GFAP; chemoresistance; functional polymorphism; glioblastoma; metastasis; miR-139

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center