Overexpressed GNA13 induces temozolomide sensitization via down-regulating MGMT and p-RELA in glioma

Yan Liu; Zepeng Du; Zhennan Xu; Tao Jin; Ke Xu; Meihui Huang; Shaohong Wang; Yuyu Zheng; Mingfa Liu; Haixiong Xu

Overexpressed GNA13 induces temozolomide sensitization via down-regulating MGMT and p-RELA in glioma

Am J Transl Res. 2021 Oct 15;13(10):11413-11426. eCollection 2021.

Authors

Yan Liu¹, Zepeng Du², Zhennan Xu¹, Tao Jin¹, Ke Xu¹, Meihui Huang², Shaohong Wang², Yuyu Zheng², Mingfa Liu¹, Haixiong Xu¹

Affiliations

¹ Department of Neurosurgery, Shantou Central Hospital Shantou 515041, China.
² Department of Pathology, Shantou Central Hospital Shantou 515041, China.

PMID: 34786068
PMCID: PMC8581860

Abstract

Temozolomide (TMZ), one of the few effective drugs used during adjuvant therapy, could effectively prolong the overall survival (OS) of glioma patients. In our previous study, the mRNA level of G Protein Subunit Alpha 13 (GNA13) was found to be inversely correlated with OS and was therefore identified as a potential biomarker for the prognosis of glioma. Henceforth, this study aims to identify the molecular mechanism of GNA13 in enhancing TMZ sensitization through bioinformatic analyses of GSE80729 and GSE43452 and other experiments. In glioma, overexpression of GNA13 downregulated PRKACA, which is a subunit of PKA, hence reducing phosphorylated RELA and MGMT. Since p-RELA and MGMT were proven to be closely associated with TMZ resistance, we therefore investigated whether thetwo signaling pathways, "GNA13/PRKACA/p-RELA", and "GNA13/PRKACA/MGMT", were involved in the molecular mechanism of GNA13 in TMZ sensitization. Our conclusion was that, GNA13 overexpression in glioma cells were more sensitive in TMZ treatment.

Keywords: GNA13; MGMT; PRKACA; RELA; glioblastoma; glioma; temozolomide (TMZ).