TBX15 facilitates malignant progression of glioma by transcriptional activation of TXDNC5
Yuyuan Ge,
Bin Jia,
Peng Zhang,
Baomin Chen,
Liang Liu,
Yan Shi,
Shilu Huang,
Xinglei Liu,
Ran Wang,
Yandong Xie,
Zhe Li,
Jun Dong
Affiliations
Yuyuan Ge
Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Bin Jia
Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China
Peng Zhang
Department of Neurosurgery, People’s Hospital of Rugao, Nantong 226500, China; Department of Neurosurgery, Rugao Clinical College, Jiangsu Health Vocational College, Nantong 226500, China
Baomin Chen
Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Liang Liu
Department of Neurosurgery, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
Yan Shi
Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Shilu Huang
Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Xinglei Liu
Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Ran Wang
Department of Neurosurgery, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
Yandong Xie
Department of Neurosurgery, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
Zhe Li
Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China
Jun Dong
Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Corresponding author
Summary: T-box transcription factor 15 (TBX15) plays important role in various cancers; however, its expression and role in glioma is still unclear. In this study, our findings indicated that TBX15 was increased in gliomas compared to normal brain tissues, and high levels of TBX15 were related to poor survival. Furthermore, TBX15 silencing in glioma cells not only inhibited their proliferation, migration, and invasion in vitro, but also weakened their ability to recruit macrophages and polarize the latter to the M2 subtype. Mechanism study indicated that thioredoxin domain containing 5 (TXNDC5) lies downstream of TBX15. Furthermore, rescue assays verified that the role of TBX15 in glioma cells is dependent on TXNDC5. Moreover, sh-TBX15 loaded into DNA origami nanocarrier suppressed the malignant phenotype of glioma in vitro and in vivo. Taken together, the TBX15/TXNDC5 axis is involved in the genesis and progression of glioma, and is a potential therapeutic target.