Li Zhiyong, Wu Shuwen, Lv Shouzheng, Wang Huili, Wang Yong, Guo Qiang
Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China.
Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China.
Biochem Biophys Res Commun. 2015 Jun 5;461(3):450-5. doi: 10.1016/j.bbrc.2015.04.013. Epub 2015 Apr 11.
Liver receptor homolog-1 (LRH-1) plays an important role in the onset and progression of many cancer types. However, the role of LRH-1 in osteosarcoma has not been well investigated. In this study, the critical role of LRH-1 in osteosarcoma cells was described. Quantitative polymerase chain reaction and Western blot analysis results revealed that LRH-1 was highly overexpressed in osteosarcoma cells. LRH-1 was knocked down by small interfering RNA (siRNA), and this phenomenon significantly inhibited osteosarcoma cell proliferation. Bioinformatics analysis results showed that LRH-1 contained putative binding sites of microRNA-451 (miR-451); this result was further validated through a dual-luciferase activity reporter assay. miR-451 was overexpressed in osteosarcoma cells through transfection of miR-451 mimics; miR-451 overexpression then significantly inhibited LRH-1 expression and cell proliferation. The loss of LRH-1 by siRNA or miR-451 mimics significantly impaired Wnt/β-catenin activity, leading to G0/G1 cell cycle arrest. Results showed that LRH-1 is implicated in osteosarcoma. Therefore, miR-451-induced suppression of LRH-1 can be a novel therapy to treat osteosarcoma.
肝脏受体同源物-1（LRH-1）在多种癌症类型的发生和发展中起重要作用。然而，LRH-1在骨肉瘤中的作用尚未得到充分研究。在本研究中，描述了LRH-1在骨肉瘤细胞中的关键作用。定量聚合酶链反应和蛋白质印迹分析结果显示，LRH-1在骨肉瘤细胞中高度过表达。通过小干扰RNA（siRNA）敲低LRH-1，这种现象显著抑制了骨肉瘤细胞增殖。生物信息学分析结果表明，LRH-1含有微小RNA-451（miR-451）的假定结合位点；这一结果通过双荧光素酶活性报告基因检测进一步得到验证。通过转染miR-451模拟物在骨肉瘤细胞中过表达miR-451；miR-451过表达随后显著抑制LRH-1表达和细胞增殖。通过siRNA或miR-451模拟物使LRH-1缺失显著损害Wnt/β-连环蛋白活性，导致G0/G1细胞周期停滞。结果表明，LRH-1与骨肉瘤有关。因此，miR-451诱导的LRH-1抑制可能是一种治疗骨肉瘤的新疗法。
