title: Suppression of liver receptor homolog-1 by microRNA-451 represses the proliferation of osteosarcoma cells.
abstract: 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.
authors: Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China.
authors: Zhiyong
authors: Z
authors: Li
authors: Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China.
authors: Shuwen
authors: S
authors: Wu
authors: Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China.
authors: Shouzheng
authors: S
authors: Lv
authors: Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China.
authors: Huili
authors: H
authors: Wang
authors: Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China.
authors: Yong
authors: Y
authors: Wang
authors: Orthopaedic Department, Tianjin Baodi Hospital, Tianjin 301800, China. Electronic address: qiangguo_gq@163.com.
authors: Qiang
authors: Q
authors: Guo
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D012516:Osteosarcoma / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*
chemical_list: C531201:MIRN451 microRNA, human; D035683:MicroRNAs; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear
keywords: Cell proliferation; Liver receptor homolog-1; Osteosarcoma; microRNA-451