A PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance
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Xiaoyan Yan1,2,5, Chuanbao Zhang2, Tingyu Liang2, Fan Yang2, Haoyuan Wang3, Fan Wu2, Wen Wang4, Zheng Wang2, Wen Cheng2, Jiangnan Xu1, Tao Jiang2, Jing Chen2 and Yaozhong Ding1
1Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
2Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China
3Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China
4Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
5The First Hospital of Baoding, Baoding, Hebei 071000, China
Yaozhong Ding, email: [email protected]
Tao Jiang, email: [email protected]
Jing Chen, email: [email protected]
Jiangnan Xu, email: [email protected]
Keywords: Collagen XVII, COL17A1, gliomas, PTEN-COL17A1, fusion
Received: November 23, 2016 Accepted: July 31, 2017 Published: August 24, 2017
Collagen XVII expression has recently been demonstrated to be correlated with the tumor malignance. While Collagen XVII is known to be widely distributed in neurons of the human brain, its precise role in pathogenesis of glioblastoma multiforme (GBM) is unknown. In this study, we identified and characterized a new PTEN-COL17A1 fusion gene in GMB using transcriptome sequencing. Although fusion gene did not result in measurable fusion protein production, its presence is accompanied with high levels of COL17A1 expression, revealed a novel regulatory mechanism of Collagen XVII expression by PTEN-COL17A1 gene fusion. Knocked down Collagen XVII expression in glioma cell lines resulted in decreased tumor invasiveness, along with significant reduction of MMP9 expression, while increased Collagen XVII expression promotes invasive activities of glioma cells and associated with GBM recurrences. Together, our results uncovered a new PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance, and demonstrated that COL17A1 could serve as a useful prognostic biomarker and therapeutic targets for GBM.
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