MicroRNA-210 is upregulated by hypoxia-inducible factor-1a in the stromal cells of giant cell tumors of bone

Abstract

To date, little is known regarding the molecular mechanisms underlying the deregulation of the giant cell tumor of bone (GCTB). Hypoxia has been confirmed to be a characteristic observed in a variety of types of cancer, and a pivotal role for hypoxia-inducible factor-1a (HIF-1a) has previously been indicated in the hypoxia adaptation of GCTBs. However, another key regulator, microRNA (miR)-210, which is closely correlated with HIF-1a, has not previously been identified in GCTBs. The present study therefore selected miR-210, the most significantly upregulated miRNA in hypoxic subtypes of cancer, for investigation in GCTB tissues. Reverse transcription-quantitative polymerase chain reaction was used to evaluate miR-210 expression levels in GCTB tissues and primary GCTB stromal cells. It was revealed that miR-210 and HIF-1a were upregulated in GCTB specimens and in primary GCTB stromal cells under hypoxia, and a positive correlation was identified between the two molecules. Furthermore, the promotion of miR-210 expression in primary GCTB stromal cells by hypoxia was HIF-1a-dependent. To the best of our knowledge, the present study was the first to identify the overexpression of miR-210 in an HIF-1a-dependent manner in GCTB specimens, suggesting an adaptive response to hypoxia in GCTB.