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TBX15通过转录激活TXDNC5促进胶质瘤的恶性进展。

TBX15 facilitates malignant progression of glioma by transcriptional activation of TXDNC5.

作者信息

Ge Yuyuan, Jia Bin, Zhang Peng, Chen Baomin, Liu Liang, Shi Yan, Huang Shilu, Liu Xinglei, Wang Ran, Xie Yandong, Li Zhe, Dong Jun

机构信息

Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China.

出版信息

iScience. 2024 Jan 18;27(2):108950. doi: 10.1016/j.isci.2024.108950. eCollection 2024 Feb 16.

DOI:10.1016/j.isci.2024.108950
PMID:38327797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10847739/
Abstract

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 , 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 and . Taken together, the TBX15/TXNDC5 axis is involved in the genesis and progression of glioma, and is a potential therapeutic target.

摘要

T盒转录因子15（TBX15）在多种癌症中发挥重要作用；然而，其在胶质瘤中的表达及作用仍不清楚。在本研究中，我们的研究结果表明，与正常脑组织相比，胶质瘤中TBX15表达增加，且高水平的TBX15与较差的生存率相关。此外，胶质瘤细胞中TBX15沉默不仅抑制其增殖、迁移和侵袭，还削弱其招募巨噬细胞并将后者极化为M2亚型的能力。机制研究表明，含硫氧还蛋白结构域5（TXNDC5）位于TBX15下游。此外，挽救实验证实TBX15在胶质瘤细胞中的作用依赖于TXNDC5。此外，装载到DNA折纸纳米载体中的sh-TBX15抑制了胶质瘤的恶性表型。综上所述，TBX15/TXNDC5轴参与胶质瘤的发生和发展，是一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/d2723eed7a88/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/515f263ad264/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/24d49789fbfe/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/27a20cca7f88/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/e2750ea0756e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/6241c525598b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/5be74c3cc631/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/b843f258ea51/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/ed360b0d7d20/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/d2723eed7a88/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/515f263ad264/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/24d49789fbfe/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/27a20cca7f88/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/e2750ea0756e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/6241c525598b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/5be74c3cc631/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/b843f258ea51/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/ed360b0d7d20/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca14/10847739/d2723eed7a88/gr8.jpg

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Gastric Cancer. 2023 Sep;26(5):798-813. doi: 10.1007/s10120-023-01409-x. Epub 2023 Jun 19.
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Characterization and clinical implications of different malignant transformation patterns in diffuse low-grade gliomas.
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Cancer Sci. 2023 Sep;114(9):3708-3718. doi: 10.1111/cas.15889. Epub 2023 Jun 18.
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Hemizygous CDKN2A deletion confers worse survival outcomes in IDHmut-noncodel gliomas.半合子CDKN2A缺失在异柠檬酸脱氢酶（IDH）突变型非编码胶质瘤中导致更差的生存结果。
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