title: Usp7 promotes medulloblastoma cell survival and metastasis by activating Shh pathway.
abstract: The ubiquitin-specific protease Usp7 plays roles in multiple cellular processes through deubiquitinating and stabilizing numerous substrates, including P53, Pten and Gli. Aberrant Usp7 activity has been implicated in many disorders and tumorigenesis, making it as a potential target for therapeutic intervention. Although it is clear that Usp7 is involved in many types of cancer, its role in regulating medulloblastoma (MB) is still unknown. In this study, we show that knockdown of Usp7 inhibits the proliferation and migration of MB cells, while Usp7 overexpression exerts an opposite effect. Furthermore, we establish Usp7 knockout MB cell line using the CRISPR/Cas9 system and further confirm that Usp7 knockout also blocks MB cell proliferation and metastasis. In addition, we reveal that knockdown of Usp7 compromises Shh pathway activity and decrease Gli protein levels, while P53 level and P53 target gene expression have no obvious changes. Finally, we find that Usp7 inhibitors apparently inhibit MB cell viability and migration. Taken together, our findings suggest that Usp7 is important for MB cell proliferation and metastasis by activating Shh pathway, and is a putative therapeutic target for MBs.
authors.affiliation: Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Zhuhai Precision Medicine Center, Zhuhai People's Hospital, Jinan University, Zhuhai, China.
authors.forename: Meixiao
authors.initials: M
authors.lastname: Zhan
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Taian, Shangdong, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Sun
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Taian, Shangdong, China.
authors.forename: Jinxiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Taian, Shangdong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Zhuhai Precision Medicine Center, Zhuhai People's Hospital, Jinan University, Zhuhai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Zhuhai Precision Medicine Center, Zhuhai People's Hospital, Jinan University, Zhuhai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Taian, Shangdong, China. Electronic address: zhouzz@sdau.edu.cn.
authors.forename: Zizhang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Zhuhai Precision Medicine Center, Zhuhai People's Hospital, Jinan University, Zhuhai, China. Electronic address: luligong1969@126.com.
authors.forename: Ligong
authors.initials: L
authors.lastname: Lu
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000502:physiology*; D000076084:Ubiquitin-Specific Peptidase 7
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7
keywords: CRISPR/Cas9; Medulloblastoma; P53; Shh; Usp7