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.
Source: Life Sciences - Category: Biology Source Type: research

Related Links:

CONCLUSIONS: These results strongly indicate that marrubenol may be considered as a potent drug lead molecule for the treatment and management of osteosarcoma. PMID: 30003743 [PubMed - in process]
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
(University of Illinois at Urbana-Champaign) A class of molecules formed when the body metabolizes omega-3 fatty acids could inhibit cancer's growth and spread, University of Illinois researchers report in a new study in mice. In mice with tumors of osteosarcoma - a bone cancer that is notoriously painful and difficult to treat -- endocannabinoids slowed the growth of tumors and blood vessels, inhibited the cancer cells from migrating and caused cancer cell death.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Publication date: October 2018Source: Biomedicine &Pharmacotherapy, Volume 106Author(s): Lingping Kong, Xin Li, Hong Wang, Guangyao He, Anzhou TangAbstractThe incidence of nasopharyngeal carcinoma (NPC) in China is relatively higher than that throughout the rest of the world, and NPC is geographically distributed. Long non-coding RNA (lncRNA) plays a key role in the development of tumors. Recent studies have found that the lncRNA Ewing sarcoma-associated transcript 1 (EWSAT1) is highly expressed in various tumors and also in NPCs. The isoflavone calycosin, which is a typical Chinese herbal medicine, can inhibit the gro...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Publication date: October 2018Source: Biomedicine &Pharmacotherapy, Volume 106Author(s): Binghua Zhou, Lijun Li, Yajing Li, Huimin Sun, Changchun ZengAbstractThe long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) overexpression was found in various tumors and the dysregulated expression of SNHG12 contributed to multidrug resistance in non-small cell lung cancer. However, the role of SNHG12 in doxorubicin resistance of osteosarcoma is still unclear. In present study, we explored the function and underlying mechanism of SNHG12 on doxorubicin resistance in osteosarcoma. High expression of SNHG12 was associated ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Publication date: 15 August 2018Source: Life Sciences, Volume 207Author(s): Hao Qu, Yue Xue, Wenwen Lian, Cong Wang, Jia He, Qihong Fu, Lijia Zhong, Nong Lin, Lihua Lai, Zhaoming Ye, Qingqing WangAbstractAimsMelatonin (N-acetyl-5-methoxytryptamine) has been reported to suppress epithelial-mesenchymal transition and cancer stem cells in some types of cancer. However, the effects of melatonin on the osteosarcoma stem cells, epithelial-mesenchymal transition and metastasis of osteosarcoma are still not clear. The present study was conducted to dissect the activity of melatonin on the osteosarcoma stem cells and the underlying...
Source: Life Sciences - Category: Biology Source Type: research
Cancer Medicine, EarlyView.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Source Type: research
Abstract Osteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti-cancer activity. To evaluate its anti-osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effec...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Publication date: Available online 9 March 2018Source: Pharmacology &TherapeuticsAuthor(s): Daniel L. Gustafson, Dawn L. Duval, Daniel P. Regan, Douglas H. ThammAbstractPet dogs are becoming increasingly recognized as a population with the potential to inform medical research through their treatment for a variety of maladies by veterinary health professionals. This is the basis of the One Health initiative, supporting the idea of collaboration between human and animal health researchers and clinicians to study spontaneous disease processes and treatment in animals to inform human health. Cancer is a major health burden...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
ConclusionsOsteosarcoma of the jaw is challenging both to diagnose and manage. This is due to the high incidence of mistakes in biopsy results, rare specific radiological features and difficulties in proper resection due to proximity to vital structures.
Source: Journal of the Egyptian National Cancer Institute - Category: Cancer & Oncology Source Type: research
ConclusionOsteosarcoma has different pathologic subtypes which correspondingly vary in their imaging criteria and their ADC values.
Source: Journal of the Egyptian National Cancer Institute - Category: Cancer & Oncology Source Type: research
More News: Biology | Bone Cancers | Cancer | Cancer & Oncology | Genetics | Osteosarcoma | Study