Guo Shibing, Bai Rui, Liu Wanlin, Zhao Aiqing, Zhao Zhenqun, Wang Yuxin, Wang Yong, Zhao Wei, Wang Wenxuan
Department of Orthopedics, Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
Department of Radiology, First Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010059, P.R. China.
Mol Med Rep. 2015 Oct;12(4):6185-92. doi: 10.3892/mmr.2015.4170. Epub 2015 Aug 3.
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-1α (HIF‑1α) has previously been indicated in the hypoxia adaptation of GCTBs. However, another key regulator, microRNA (miR)‑210, which is closely correlated with HIF‑1α, 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‑1α 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‑1α‑dependent. To the best of our knowledge, the present study was the first to identify the overexpression of miR‑210 in an HIF‑1α‑dependent manner in GCTB specimens, suggesting an adaptive response to hypoxia in GCTB.
迄今为止，关于骨巨细胞瘤（GCTB）失调的分子机制仍知之甚少。缺氧已被证实在多种癌症类型中都有表现，并且先前已表明缺氧诱导因子-1α（HIF-1α）在GCTB的缺氧适应中起关键作用。然而，另一个关键调节因子，即与HIF-1α密切相关的微小RNA（miR）-210，此前尚未在GCTB中被发现。因此，本研究选择了癌症缺氧亚型中上调最显著的miR-210，对GCTB组织进行研究。采用逆转录定量聚合酶链反应来评估GCTB组织和原代GCTB基质细胞中miR-210的表达水平。结果显示，在缺氧条件下，GCTB标本和原代GCTB基质细胞中miR-210和HIF-1α均上调，且这两种分子之间存在正相关。此外，缺氧对原代GCTB基质细胞中miR-210表达的促进作用依赖于HIF-1α。据我们所知，本研究首次在GCTB标本中发现miR-210以HIF-1α依赖的方式过表达，提示GCTB对缺氧的适应性反应。
