title: CSE1L interaction with MSH6 promotes osteosarcoma progression and predicts poor patient survival.
abstract: To discover tumor-associated proteins in osteosarcoma, a quantitative proteomic analysis was performed to identify proteins that were differentially expressed between osteosarcoma and human osteoblastic cells. Through clinical screening and a functional evaluation, chromosome segregation 1-like (CSE1L) protein was found to be related to the growth of osteosarcoma cells. To date, little is known about the function and underlying mechanism of CSE1L in osteosarcoma. In the present study, we show that knockdown of CSE1L inhibits osteosarcoma growth in vitro and in vivo. By co-immunoprecipitation and RNA-seq analysis, CSE1L was found to interact with mutS homolog 6 (MSH6) and function as a positive regulator of MSH6 protein in osteosarcoma cells. A rescue study showed that decreased growth of osteosarcoma cells by CSE1L knockdown was reversed by MSH6 overexpression, indicating that the activity of CSE1L was an MSH6-dependent function. In addition, depletion of MSH6 hindered cellular proliferation in vitro and in vivo. Notably, CSE1L expression was correlated with MSH6 expression in tumor samples and was associated with poor prognosis in patients with osteosarcoma. Taken together, our results demonstrate that the CSE1L-MSH6 axis has an important role in osteosarcoma progression.
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
authors.forename: He-Chun
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Qing-Cheng
authors.initials: QC
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Cun-Yi
authors.initials: CY
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D029563:Cellular Apoptosis Susceptibility Protein / Q000378:metabolism*; D002648:Child; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011485:Protein Binding; D020543:Proteome; D040901:Proteomics; D012008:Recurrence; D055815:Young Adult
chemical_list: D015415:Biomarkers; D029563:Cellular Apoptosis Susceptibility Protein; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D020543:Proteome