DEC2 expression is positively correlated with HIF-1 activation and the invasiveness of human osteosarcomas

• DOI: 10.1186/s13046-015-0135-8
• Publication Date: 2015-02-27T12:00:45Z
• Authors: Tu Hu; Nengbin He; Yunsong Yang; Chengqian Yin; Nianli Sang; Qingcheng Yang
• Keywords: Osteosarcoma; 0303 health sciences; Protein Stability; Gene Expression; Bone Neoplasms; Hypoxia-Inducible Factor 1, alpha Subunit; Prognosis; Models, Biological; 3. Good health; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Gene Knockdown Techniques; Basic Helix-Loop-Helix Transcription Factors; Humans; RNA Interference; Hypoxia-Inducible Factor 1; RNA, Small Interfering; Hypoxia; Research Article

Osteosarcoma is the most common malignancy of bone. HIF-1 (hypoxia-inducible factor 1) activation critical for metabolic reprogramming and progression solid tumors, DEC2 (differentiated embryonic chondrocyte gene 2) has been recently reported to suppress in human breast endometrial cancers. However, roles osteosarcomas remain unclear. We evaluated correlation expression prognosis, studied invasiveness osteosarcoma. Multiple approaches including immunohistochemical staining clinical osteosarcoma tissues, siRNA-based knockdown other molecular biology techniques were used. Particularly, by using a repetitive trans-well culture-based vitro evolution system, we selected more invasive subpopulation (U2OS-M) cells from U2OS used it as model study found that was positively correlated with HIF-1α levels, poor prognosis osteosarcomas. cell lines (U2OS, MNNG 143B) attenuated accumulation impaired up-regulation target genes response hypoxia. Compared low parental U2OS, U2OS-M showed higher levels which confirmed at both mRNA protein levels. Importantly, increased resulted rapid Finally, sufficient upregulate cells. Taken together, whereas promote degradation types our data indicate facilitates stabilization promotes This implies may contribute metastasis sensitizing tumor On hand, first demonstration novel DEC2-HIF-1 vicious cycle tumor-type specific role DEC2.