RESUMEN
CSN5, a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), functions as a potential tumor promoter in various cancers. However, the biological functions and clinical significance of CSN5 in osteosarcoma (OS) remains unclear. Here, we report that OS tumors overexpressed CSN5 compared with normal bone tissues, and CSN5 overexpression was obviously associated with the malignant phenotype and poor prognosis in patients with OS. In addition, high CSN5 expression significantly promoted the growth of OS cells, whereas CSN5 silence suppressed the tumorigenicity of OS cells. Furthermore, we found PI3K/Akt signaling pathway contributed to the effects of CSN5 in OS cells, and blocking the Akt pathway significantly inhibited the actions of CSN5. Mechanistically, we demonstrate that CSN5 positively regulated EGFR stability through reducing the levels of EGFR ubiquitination, thereby activating the PI3K/Akt signaling pathway in OS cells. Moreover, our results shown that the oncogenic effects of CSN5 on OS cells were EGFR dependent. Thus, CSN5 has a central role in regulating diverse aspects of the pathogenesis of OS, which could be a potential diagnostic and therapeutic target for OS.
Asunto(s)
Complejo del Señalosoma COP9/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Osteosarcoma/genética , Osteosarcoma/patología , Péptido Hidrolasas/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/genética , Animales , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular , Línea Celular Tumoral , Proliferación Celular/genética , Receptores ErbB/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ubiquitinación/genéticaRESUMEN
INTRODUCTION: Randomised controlled trials (RCTs) have reported conflicting results on whether extracorporeal shock wave therapy alleviates the pain of recalcitrant plantar fasciitis patients. We focused on high-energy extracorporeal shock wave therapy (HESWT) and aimed to assess the effectiveness and feasibility of HESWT versus placebo in the treatment of recalcitrant plantar fasciitis. PATIENTS AND METHODS: We reviewed all RCTs comparing HESWT and placebo from PubMed, EMBASE, Cochrane Central Register of Controlled Trials and also the reference lists of articles. We used a fixed-effects model or a random model depending on heterogeneity and estimated the odds radio (OR) and 95% confidence interval (95% CI). Study quality was assessed using the Jadad scale. RESULTS: Five placebo-controlled and double-blinded clinical trials including 716 patients were included. Overall, the quality of the trials was good, and a test for heterogeneity confirmed the presence of little heterogeneity (p = 0.31, I2 = 16%). The pooled OR from the five trials was estimated to be 2.25 (95% CI, 1.66-3.06; p <0.00001) at 12 weeks after active treatment. CONCLUSION: The results of the meta-analysis provide strong evidence that HESWT was effective in the treatment of recalcitrant plantar fasciitis when compared with placebo. We recommend HESWT as a remedial measure after failure of traditional conservative treatment and ahead of surgical intervention.