High mobility group box 2 modulates the progression of osteosarcoma and is related with poor prognosis

Background: Increased expression of high mobility group box 2 (HMGB2) has been reported to promote the progression of several malignancies and be related to poor outcome. However, few studies have explored the relationship between HMGB2 and osteosarcoma. In this study, we aimed to obtain a better understanding of HMGB2 and its function in osteosarcoma.

Methods: Utilizing osteosarcoma paraffin sections and osteosarcoma cell lines, we observed the clinico-pathological relationship of osteosarcoma with HMGB2 expression and investigated the functions of HMGB2 in vitro. The possible pathways and regulation networks in which HMGB2 is involved were further explored through analysis of miRNA, mRNA and lncRNA micro array data sets.

Results: Strong expression of HMGB2 was found to be related with Enneking staging (P=0.002), tumor size (P=0.006), metastasis (P<0.001), and survival (P=0.011) in osteosarcoma. Multivariate analysis revealed that HMGB2 might have independent prognostic value in osteosarcoma (P=0.022). Kaplan-Meier curves and the log-rank test showed that survival time was significantly reduced in OS patients with strong HMGB2 expression (P=0.0056). In vitro experiments showed that HMGB2 overexpression promoted cell proliferation and enhanced the migration and invasion ability of osteosarcoma cells. Gene Ontology (GO) term analysis of osteosarcoma cell lines revealed HMGB2 to have various functions and to be mainly enriched in regulation of cell proliferation, cell death, and DNA binding. A competing endogenous RNA (ceRNA) network of miR-139-5p and six candidate lncRNAs was also suggested as targeting HMGB2 in osteosarcoma.

Conclusions: Our findings suggest that HMGB2 might have various functions in promoting the progression of osteosarcoma and may serve as a new target for osteosarcoma research.