title: Mediator of RNA polymerase II transcription subunit 19 promotes osteosarcoma growth and metastasis and associates with prognosis.
abstract: Osteosarcoma (OS) is the most common primary malignant tumour of bone. Nearly 30-40% of OS patients have a poor prognosis despite multimodal treatments. Because the carcinogenesis of OS remains unclear, the identification of new oncogenes that control the tumourigenesis and progression of OS is crucial for developing new therapies. Here, we found that the expression of Mediator of RNA polymerase II transcription subunit 19 (Med19) was increased in OS samples from patients compared to normal bone tissues. Cyclin D1 and cyclin B1 are upregulated in Med19 positive OS tissues. Importantly, among 97 OS patients of Enneking stage IIB or IIIB, Med19 expression was correlated with metastasis (P<0.05) and poor prognosis (P<0.01). Med19 knockdown significantly induced growth inhibition, reduced colony-forming ability and suppressed migration in the OS cell lines Saos-2 and U2OS, along with the downregulated expression of cyclin D1 and cyclin B1. Med19 knockdown also induced apoptosis in Saos-2 cells via induction of caspase-3 and poly ADP-ribose polymerase (PARP). In addition, Med19 knockdown significantly suppressed tumour growth in an OS xenograft nude mouse model via suppression of cyclin D1 and cyclin B1. Simultaneously, Med19 downregulation decreased the expression of Ki67 and proliferating cell nuclear antigen (PCNA) in tumour samples from OS xenograft nude mice. Med19 depletion remarkably reduced tumour metastasis in a model of OS metastatic spreading. Taken together, our data suggest that Med19 acts as an oncogene in OS via a possible cyclin D1/cyclin B1 modulation pathway.
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Wenxi
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Zhichang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Daliu
authors.initials: D
authors.lastname: Min
authors.affiliation: Department of Orthopedics, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Yuanjue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Shuier
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Aina
authors.initials: A
authors.lastname: He
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, 200233 Shanghai, People's Republic of China. Electronic address: shenzanok@yahoo.com.
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D056892:Mediator Complex / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D055815:Young Adult
chemical_list: D056744:Cyclin B1; C558319:MED19 protein, human; D056892:Mediator Complex; D019938:Cyclin D1
keywords: Lentivirus; Med19; Oncogene; Osteosarcoma; RNA interference