TMEM2 induces epithelial-mesenchymal transition and promotes resistance to temozolomide in GBM cells

Lun Gao; Shiao Tong; Junhui Liu; Jiayang Cai; Zhang Ye; Long Zhou; Ping Song; Zhiyang Li; Pan Lei; Hangyu Wei; Qiuwei Hua; Daofeng Tian; Qiang Cai

doi:10.1016/j.heliyon.2023.e16559

TMEM2 induces epithelial-mesenchymal transition and promotes resistance to temozolomide in GBM cells

Heliyon. 2023 May 24;9(6):e16559. doi: 10.1016/j.heliyon.2023.e16559. eCollection 2023 Jun.

Authors

Lun Gao^{1

2}, Shiao Tong^{1

2}, Junhui Liu^{1

2}, Jiayang Cai^{1

2}, Zhang Ye^{1

2}, Long Zhou^{1

2}, Ping Song^{1

2}, Zhiyang Li^{1

2}, Pan Lei^{1

2}, Hangyu Wei^{1

2}, Qiuwei Hua^{1

2}, Daofeng Tian^{1

2}, Qiang Cai^{1

2}

Affiliations

¹ Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
² Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract

Glioblastoma multiforme (GBM) is the most common intracranial malignant tumor and is notorious for its poor prognosis. An important element in the short overall survival of GBM patients is the lack of understanding the pathogenesis and progression of tumor and deficiency biomarkers that can be used for early diagnosis and therapeutic sensitivity monitoring. Studies have shown that transmembrane protein 2 (TMEM2) is participated in tumorigenesis of various human tumors, including rectal and breast cancers. Although Qiuyi Jiang et al. have reported that TMEM2 combined with IDH1/2 and 1p19q can predict the survival time of glioma patients based on bioinformatics, its expression and biological role of glioma remain unclear. In our study, we investigated the effect of TMEM2 expression level on glioma malignancy in public datasets and an independent internal dataset. We revealed TEMM2 expression was higher in GBM tissues than in non-tumor brain tissues (NBT). Moreover, the increase in TMEM2 expression level was closely related to tumor malignancy. The survival analysis showed that TMEM2 high expression reduces survival time in all glioma patients, including GBM and LGG patients. Subsequent experiments demonstrated that knockdown TMEM2 inhibited proliferation of GBM cells. In addition, we analyzed TMEM2 mRNA levels in different GBM subtypes, and demonstrated that TMEM2 expression was upregulated in mesenchymal subtype. Meanwhile, bioinformatics analysis and transwell assay indicated that knockdown TMEM2 suppressed epithelial-mesenchymal transition (EMT) in GBM. Importantly, Kaplan-Meier analysis demonstrated that TMEM2 high expression reduced the treatment response to TMZ in GBM patients. Knockdown of TMEM2 alone did not reduce apoptosis GBM cells, but significant apoptotic cells were observed in the group treated with additional TMZ. These studies may contribute to improving the accuracy of early diagnosis and evaluating the effectiveness of TMZ treatment in GBM patients.

Keywords: EMT; Prognosis; Proliferation; TMEM2; TMZ.