Overexpression of GRIM-19 accelerates radiation-induced osteosarcoma cells apoptosis by p53 stabilization
This study was designed to investigate the role and the underlying mechanism of GRIM-19 in osteosarcoma progression.Materials and methodsOsteosarcoma tissues and cell lines were utilized to analyze the expressions of GRIM-19 in osteosarcoma by qRT-PCR and Western blot. Methods containing flow cytometry, irradiation exposure, cells inoculation, plasmid transfection, and protein immunoprecipitation were used to investigate the underlying mechanisms of GRIM-19 in osteosarcoma progression.Key findingsGRIM-19 is downregulated in osteosarcoma tissues and cell lines. Exposure to radiation induces osteosarcoma cell apoptosis by upregulation of p53 both in U2OS (p53-wt) and exogenous p53-introduced MG-63 (p53-null) osteosarcoma cells. Overexpression of GRIM-19 accelerates radiation-induced osteosarcoma cells apoptosis by p53 stabilization ex vivo and in vivo. Mechanistically, forced expression of GRIM-19 diminishes the activity of E3 ubiquitin-protein ligase mouse double minute 2 homolog (MDM2), a specific p53 protease, results in the accumulation of p53 and activation of p53-mediated apoptosis.SignificanceGRIM-19 was proved to modulate radiation-induced osteosarcoma cells apoptosis in a p53 dependent manner by mediating MDM2 activity, which sheds light on the development of GRIM-19-based molecular target therapy on osteosarcoma.
CONCLUSIONS: Low expression of miR-340-5p in OS and U2OS cells could inhibit the course of OS by negatively regulating Wnt/β-catenin signaling pathway through targeting STAT3 gene. Therefore, miR-340-5p might be a potential biomarker and target for the diagnosis and treatment of OS. PMID: 30779064 [PubMed - in process]
CONCLUSIONS Functional genetic polymorphisms in CDKN2A/B predict the susceptibility and outcome of osteosarcoma in Chinese individuals. PMID: 30774116 [PubMed - in process]
Osteosarcoma strikes hundreds of people each year, of both advanced and younger ages, and is often terminal. Like many tumor types, these bone tumors will frequently undergo a neuroendocrine transition, utiliz...
In conclusion, these findings indicate that miR-876-5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS. PMID: 30773847 [PubMed - as supplied by publisher]
AbstractPrimary osteosarcoma of sphenoid and ethmoid sinus present as a challenge in head neck cancer. A 17 year female presented with left sided hemifacial pain, headache with nasal discharge. Clinico-radiological finding showed mass in sphenoethmoid recess spreading to adjacent structures. Endoscopic resection was done. Histopathological diagnosis was osteosarcoma of sphenoid and ethmoid sinus. Adjuva nt chemotherapy administered. Osteosarcomas of sphenoid and ethmoid sinus are aggressive tumors with variable clinical features warranting high clinical suspicion.
This study aims to investigate the role of microRNA-92a (miR-92a) in metastasis of osteosarcoma (OS) cells in vivo and in vitro by regulatingTCF21 with the transmission of bone marrow derived mesenchymal stem ...
Abstract Aberrant miRNAs play important roles in tumor development and progression. Previous studies reported that miR-552 was dysregulated expressed in multiple cancers. However, its biological effects and underlying mechanism in osteosarcoma remains largely unknown. In present research, we demonstrated that miR-552 was significantly up-regulated in both osteosarcoma cell lines and tissues for the first time. Its high-expression was significantly associated with poor prognostic features and overall survival of osteosarcoma patients. Gain- and loss-of-function experiment confirmed that miR-552 promoted cell migrat...
Conclusions: Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS. PMID: 30719181 [PubMed - in process]
CONCLUSIONS: The first evaluation of the safety and efficacy of an alpha particle in high-risk osteosarcoma shows that the recommended phase II dose for 223RaCl2 in osteosarcoma is 100 kBq/kg monthly (twice the dose approved for prostate cancer), with minimal hematologic toxicity, setting the stage for combination therapies. PMID: 30733229 [PubMed - as supplied by publisher]