ABSTRACT
Osteosarcoma(OS)is a malignant tumor that occurs mostly in children and adolescents with a poor prognosis. The 5-year survival rate and the survival rate of patients with lung metastasis or distant metastasis are still unsatisfactory. Currently,the treatment of osteosarcoma is still unsatisfactory under the bottleneck period. Long-chain non-coding RNA(LncRNA)is a non-pro-tein-encoding RNA molecule involved in a variety of processes including gene expression,chromatin remodeling,post-transcription-al processing and transcription. LncRNAs are abnormally expressed in human cancers and they are involved in tumor development, progression and metastasis. This article reviews the research progress of long-chain non-coding RNA in osteosarcoma,which is in-tended to provide further research for osteosarcoma and propose new diagnosis and treatment strategies.
ABSTRACT
Objective To investigate the role of glycogen synthase kinase -3beta(GSK3β)on invasion and metastasis of human osteosarcoma cells .Methods Expression and phosphorylation of GSK 3βwere examined in osteosarcoma cell lines and tumor tissue from osteosarcoma patients by Western blot .The effects of small mole-cule GSK3βinhibitors on cell metastasis were detected by cell invasion assay and cell migration assay .Results Osteosarcoma cell lines showed increased GSK 3βexpression and abnormal activity regulation .In tumor tissue of patients with osteosarcoma metastasis and non -metastasis,GSK3βwere detected expression and abnormal activi-ty,especially in tumor tissue of the patients with osteosarcoma metastasis .Inhibition of GSK3βactivity resulted in inhibiting cells invasion and migration in osteosarcoma cell line .Conclusion In this research,we demonstrated that GSK3βencouraged osteosarcoma cells metastasis .The result will open up a potential target for clinical treat-ment of osteosarcoma .
ABSTRACT
Objective To explore SIRT4 gene expression in tumor tissue and investigate the clinicol-pathological features in osteosarcoma .Methods In this study ,SIRT4 protein expression was detected in 106 os-teosarcoma tissues and 36 paired neighboring non -tumorous tissues by immunohistochemistry and determined the correlation between the SIRT 4 expression and the clinicopathological features .Results SIRT4 protein was dra-matically decreased in osteosarcoma cells compared with neighboring non -tumorous bone cells .The low expres-sion of SIRT4 was notably associated with a poor overall survival and disease -free survival in osteosarcoma pa-tients.By using univariate and multivariate analyses ,we confirmed that the increased SIRT 4 expression was an in-dependent factor in predicting better prognosis for patients .Conclu is on SIRT4 expression might be an inde-pendent biomarker for prognostic evaluation of osteosarcoma .
ABSTRACT
Objective To investigate the molecular mechanisms of effect of glycogen synthase kinase -3beta( GSK3β) on proliferation of human osteosarcoma cells .Methods Normal osteoblast hFO and osteosarcoma cell lines were examined for GSK 3βexpression and activity by Western blot and in vitro kinase assay ( NIRKA) . The effects of small molecule GSK3βinhibitors on cell proliferation and apoptosis were examined .Depletion of en-dogenous GSK3βby GSK 3βsiRNA detected the expression and phosphorylation of p 27 and its downstream cy-clinD1-CDK-Rb pathway factor by Western blot .Human osteosarcoma cell xenografts ,in athymic mice model , were treated with DMSO as control or with GSK 3βinhibitor SB-216763 or AR-A014418 by intraperitoneal in-jection,3 times a week.The tumor growth and body weight were observed in nude mice .Results Osteosarcoma cell lines showed increased GSK 3βexpression and decreased serine 9 phosphorylation compared with normal oste-oblast cells.Inhibition of GSK3βresulted in attenuated cell proliferation and increased apoptosis in most osteosar-coma cell lines in vitro and in vivo in MG 63 xenografts in rodents but not in hFOB cells .We decreased endoge-nous GSK3b activity,tumor growth was inhibited in SB216763,AR -A014418 group compared with control group.There was statistical significance(P<0.05).GSK3βinhibition in osteosarcoma cells was associated with decreased p27 expression, Rb expression and phosphorylation level of decline , CDK2, 4, 6 protein level de-creased,the upregulation of cyclin D1 expression but the phosphorylation level of no effect .Conclusion In this research,we demonstrate that deregulated GSK 3βsustains osteosarcoma cells survival through modulation of p27and cyclinD1-CDK-Rb pathway.The result will open up a potential target for clinical treatment of osteosar -coma.
ABSTRACT
Osteosarcoma is a common malignant bone tumor in the skeletal system of minors .The five-year survival rate of patients with osteosarcoma is significanty improved by neoadjuvant chemotherapy combined with surgery.However,its mortality and morbidity rates remain quite high .With the development of molecular bi-ology and genetics ,gene therapy provides a new hope for patients with osteosarcoma .Researchers at home and a-broad have actively explored effective therapeutic targets .In this paper ,new progress in the study of gene -targe-ted therapy for osteosarcoma is reviewed .