title: Heterogeneous expression and biological function of ubiquitin carboxy-terminal hydrolase-L1 in osteosarcoma.
abstract: Ubiquitin carboxyl terminal hydrolase 1 (UCHL1), a member of the UCH class of DUBs, has been reported as either an oncogene or a tumor suppressor. However, the molecular mechanism underlying the biological function of UCHL1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of UCHL1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that UCHL1 was elevated in osteosarcoma compared with normal bone tissue. Moreover, UCHL1 expression level was correlated with tumor maximum diameter, high rate of lung metastases and short survival time. Then, we found that knockdown of UCHL1 in osteosarcoma cell MG63 inhibited cell proliferation and significantly increased cell population in the G1 phase. Several cyclins promoting G1/S phase transition were reduced after UCHL1 knockdown, including cell cycle regulator cyclin D1, cyclin E1 and CDK6. Moreover, inhibition of UCHL1 in MG63 cells dramatically induced cell apoptosis. We also found that down-regulation of UCHL1 in MG63 significantly inhibited cell invasion. Then, we found that there was a positive correlation between UCHL1 expression level and the Akt and ERK phosphorylation status. Finally, in vivo data showed that knockdown of UCHL1 inhibited osteosarcoma growth in nude mice. These results indicate that UCHL1 could work as an oncogene and may serve as a promising therapeutic strategy for osteosarcoma.
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Shuier
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Guanglei
authors.initials: G
authors.lastname: Qiao
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Daliu
authors.initials: D
authors.lastname: Min
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Zhichang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yuanjue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Wenxi
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: zse78106@qq.com.
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: zse78106@qq.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000378:metabolism; D012516:Osteosarcoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C530104:CCND1 protein, human; C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; C482860:UCHL1 protein, human; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D048049:Extracellular Signal-Regulated MAP Kinases; D043222:Ubiquitin Thiolesterase
keywords: Akt; Invasion; MAPK/ERK; Osteosarcoma; Proliferation; UCHL1