Hu Jun, Lv Guohua, Zhou Shuguang, Zhou Yucheng, Nie Bangxu, Duan Hong, Zhang Yunfeng, Yuan Xiaofeng
Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Orthopedics, The First Hospital of Kunming, Kunming, Yunnan, China.
Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
PLoS One. 2015 May 14;10(5):e0121175. doi: 10.1371/journal.pone.0121175. eCollection 2015.
Osteosarcoma is the most common primary bone malignancy in children and young adults. Increasing results suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for osteosarcoma.
MiR-182 expression level in osteosarcoma cell lines and tissues were assayed by qRT-PCR. MiRNA mimics or inhibitor were transfected for up-regulation or down-regulation of miR-182 expression. Cell function was assayed by CCK8, migration assay and invasion assay. The target genes of miR-182 were predicated by bioinformatics algorithm (TargetScan Human).
MiR-182 was down-regulated in osteosarcoma tissues and cell lines. Overexpression of miR-182 inhibited tumor growth, migration and invasion. Subsequent investigation revealed that TIAM1 was a direct and functional target of miR-182 in osteosarcoma cells. Overexpression of miR-182 impaired TIAM1-induced inhibition of proliferation and invasion in osteosarcoma cells.
Down-expression of miR-182 in osteosarcoma promoted tumor growth, migration and invasion by targeting TIAM1. MiR-182 might act as a tumor suppressor gene whose down-regulation contributes to the progression and metastasis of osteosarcoma, providing a potential therapy target for osteosarcoma patients.
骨肉瘤是儿童和年轻成年人中最常见的原发性骨恶性肿瘤。越来越多的研究结果表明,微小RNA(miRNA)的发现可能为骨肉瘤提供一种新的治疗靶点。
采用qRT-PCR检测骨肉瘤细胞系和组织中miR-182的表达水平。转染miRNA模拟物或抑制剂以上调或下调miR-182的表达。通过CCK8、迁移实验和侵袭实验检测细胞功能。通过生物信息学算法(TargetScan Human)预测miR-182的靶基因。
miR-182在骨肉瘤组织和细胞系中表达下调。miR-182的过表达抑制肿瘤生长、迁移和侵袭。后续研究表明,TIAM1是骨肉瘤细胞中miR-182的直接功能靶点。miR-182的过表达削弱了TIAM1诱导的骨肉瘤细胞增殖和侵袭抑制。
骨肉瘤中miR-182的低表达通过靶向TIAM1促进肿瘤生长、迁移和侵袭。miR-182可能作为一种肿瘤抑制基因,其下调促进骨肉瘤的进展和转移,为骨肉瘤患者提供了潜在的治疗靶点。