HMGB1 promotes cellular proliferation and invasion, suppresses cellular apoptosis in osteosarcoma

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence indicated that the deregulation of DNA-bindi...

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Published in:	Tumor biology Vol. 35; no. 12; pp. 12265 - 12274
Main Authors:	Meng, Qingbing, Zhao, Jie, Liu, Hongbing, Zhou, Guoyou, Zhang, Wensheng, Xu, Xingli, Zheng, Minqian
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer Netherlands 01-12-2014 Springer Nature B.V
Subjects:	Adolescent Adult Apoptosis - genetics Biomedicine Bone cancer Bone Neoplasms - genetics Bone Neoplasms - metabolism Bone Neoplasms - pathology Cancer Research Caspase 3 - genetics Caspase 3 - metabolism Cell Cycle - genetics Cell Line, Tumor Cell Proliferation Cell Survival - genetics Cellular biology Cyclin D1 - genetics Cyclin D1 - metabolism Female Gene Expression Regulation, Neoplastic HMGB1 Protein - genetics HMGB1 Protein - metabolism Humans Male Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - metabolism Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Staging Osteosarcoma - genetics Osteosarcoma - metabolism Osteosarcoma - pathology Pathology Proteins Research Article Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism Young Adult Osteosarcoma RNA interference HMGB1
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Summary:	Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence indicated that the deregulation of DNA-binding protein high-mobility group box 1 (HMGB1) was associated with the development of cancer. This study aimed to explore the expression of HMGB1 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the role of HMGB1 in the development of osteosarcoma. The results from RT-PCR and Western blot showed that the expression rate of HMGB1 messenger RNA (mRNA) and the expression of HMGB1 in the osteosarcoma tissues were significantly higher than those in normal bone tissue ( p < 0.05), the expression rate of HMGB1 mRNA and the expression of HMGB1 in the carcinoma tissues with positive lung metastasis were significantly higher than those without lung metastasis ( p < 0.05), and with increasing Enneking stage, the expression rate of HMGB1 mRNA and the expression of HMGB1 also increased ( p < 0.05). In order to explore the role of HMGB1 in osteosarcoma, the expression of HMGB1 in the human osteosarcoma MG-63 cell line was downregulated by the technique of RNA interference. Western blot results showed that the protein expression of HMGB1 was significantly decreased in the MG-63 cells from HMGB1-siRNA transfection group ( p < 0.05), which suggested that HMGB1 was successfully downregulated in the MG-63 cells. Then the changes in proliferation, apoptosis, and invasion of MG-63 cells were examined by MTT test, PI staining, annexin V staining, and transwell chamber assay. Results showed that the abilities of proliferation and invasion were suppressed in HMGB1 knockdown MG-63 cells, and the abilities of apoptosis were enhanced in HMGB1 knockdown MG-63 cells. The expression of cyclin D1, MMP-9 was downregulated in HMGB1 knockdown MG-63 cells, and the expression of caspase-3 was upregulated in HMGB1 knockdown MG-63 cells. Taken together, the overexpression of HMGB1 in osteosarcoma might be related to the tumorigenesis, invasion, and metastasis of osteosarcoma, which might be a potential target for the treatment of osteosarcoma.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1010-4283 1423-0380
DOI:	10.1007/s13277-014-2535-3