Xu Honghai, Liu Cong, Zhang Yuelin, Guo Xiong, Liu Zongzhi, Luo Zhenqun, Chang Yanhai, Liu Shizhang, Sun Zhengming, Wang Xiaoqing
Department of Orthopaedics, the Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Medical College of Xi'an Jiaotong University, Xi'an 710068, China.
Xi'an Medical University, Xi'an 710021, China.
Acta Biochim Biophys Sin (Shanghai). 2014 Nov;46(11):965-72. doi: 10.1093/abbs/gmu089. Epub 2014 Sep 30.
Multiple myeloma (MM) is the most common cause of death from hematological malignancy worldwide, and recent studies have revealed that let-7b-5p can play an inhibitory role in tumorigenesis. However, the role of let-7b-5p in MM still remains unclear. The aim of this study was to elucidate the molecular mechanisms by which let-7b-5p acts as a tumor suppressor in MM. Here, quantitative real-time polymerase chain reaction results showed that the expression of let-7b-5p was remarkably reduced in MM tissues and MM cell lines (RPMI-8226 and U266 cells). Furthermore, over-expression of let-7b-5p significantly suppressed RPMI-8226 cell proliferation and induced S/G2 cell cycle arrest and apoptosis. Luciferase reporter assay results demonstrated that insulin-like growth factor receptor 1 (IGF1R) was negatively regulated by let-7b-5p at the post-transcriptional level. The mRNA and protein levels of IGF1R in RPMI-8226 cells were down-regulated by let-7b-5p. Furthermore, the cell phenotype altered by let-7b-5p inhibitor can be rescued by IGF1R silencing (si-IGF1R). Taken together, our results demonstrated that let-7b-5p functions as a tumor suppressor in MM, suggesting that let-7b-5p may be a potential therapeutic target for MM.
多发性骨髓瘤（MM）是全球血液系统恶性肿瘤最常见的死亡原因，最近的研究表明，let-7b-5p在肿瘤发生中可发挥抑制作用。然而，let-7b-5p在MM中的作用仍不清楚。本研究的目的是阐明let-7b-5p在MM中作为肿瘤抑制因子发挥作用的分子机制。在此，定量实时聚合酶链反应结果显示，let-7b-5p在MM组织和MM细胞系（RPMI-8226和U266细胞）中的表达显著降低。此外，let-7b-5p的过表达显著抑制RPMI-8226细胞增殖，并诱导S/G2期细胞周期阻滞和细胞凋亡。荧光素酶报告基因检测结果表明，胰岛素样生长因子受体1（IGF1R）在转录后水平受到let-7b-5p的负调控。let-7b-5p下调了RPMI-8226细胞中IGF1R的mRNA和蛋白水平。此外，let-7b-5p抑制剂改变的细胞表型可通过IGF1R沉默（si-IGF1R）得到挽救。综上所述，我们的结果表明let-7b-5p在MM中作为肿瘤抑制因子发挥作用，提示let-7b-5p可能是MM的潜在治疗靶点。
