PTBP3通过稳定Twist1促进胶质母细胞瘤的肿瘤发生。

PTBP3 promotes tumorigenesis of glioblastoma by stabilizing Twist1.

作者信息

Xie Peng, Zhang Yueqing, Chen Rui, Zheng Jinyu, Cui Gang

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China; Department of Neurosurgery, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, No.62, Huaihai Road(S.), Huai'an, Jiangsu 223002, P.R. China.

Department of Neurosurgery, Huai'an Cancer Hospital, No19 shanyang Road, Huai'an, Jiangsu 223200, P.R. China.

出版信息

Transl Oncol. 2022 Nov;25:101520. doi: 10.1016/j.tranon.2022.101520. Epub 2022 Aug 17.

DOI:10.1016/j.tranon.2022.101520

PMID:35987089

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9411677/

Abstract

OBJECTIVE

Glioblastoma (GBM) is the most common malignancy tumor of central nervous system. PTBP3 was closely associated with the development of tumor. However, the function and molecular mechanism of PTBP3 in GBM is little known.

METHODS

qPCR and immunoblotting were used to detect PTBP3 expression levels in glioma tissues and cells. CCK8, Edu, flow cytometry, wound healing, and transwell assays were used to examined the function of PTBP3 in GBM. qPCR, Immunoblotting, and ubiquitination assays were performed to identify the mechanism of PTBP3.

RESULTS

We found that PTBP3 was upregulated in GBM, and high expression of PTBP3 correlated with the poor survival of GBM patients. PTBP3 knockdown reduced proliferation, invasion, and migration of GBM. Conversely, overexpressing PTBP3 has an opposite effect. Moreover, PTBP3 had an effect on the EMT of GBM. More importantly, we found that PTBP3 stabilized Twist1 by decreasing its ubiquitination and degradation. Furthermore, orthotopic xenograft models were used to demonstrate the PTBP3 on the development of GBM in vivo.

CONCLUSION

This study proved that PTBP3 promoted tumorigenesis of GBM by stabilizing Twist1, which provided a new therapeutic target for GBM.

摘要

目的

胶质母细胞瘤（GBM）是中枢神经系统最常见的恶性肿瘤。PTBP3与肿瘤的发生发展密切相关。然而，PTBP3在GBM中的功能和分子机制尚不清楚。

方法

采用qPCR和免疫印迹法检测胶质瘤组织和细胞中PTBP3的表达水平。采用CCK8、Edu、流式细胞术、伤口愈合和transwell实验检测PTBP3在GBM中的功能。通过qPCR、免疫印迹和泛素化实验确定PTBP3的作用机制。

结果

我们发现PTBP3在GBM中上调，且PTBP3的高表达与GBM患者的不良预后相关。敲低PTBP3可降低GBM的增殖、侵袭和迁移能力。相反，过表达PTBP3则有相反的效果。此外，PTBP3对GBM的上皮-间质转化有影响。更重要的是，我们发现PTBP3通过减少Twist1的泛素化和降解来使其稳定。此外，利用原位异种移植模型在体内证明了PTBP3对GBM发生发展的影响。