Let-7b-5p regulates proliferation and apoptosis in multiple myeloma by targeting IGF1R

Honghai Xu, Cong Liu, Yuelin Zhang, Xiong Guo, Zongzhi Liu, Zhenqun Luo, Yanhai Chang, Shizhang Liu, Zhengming Sun and Xiaoqing Wang

Department of Orthopaedics, the Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Medical College of Xi'an Jiaotong University, Xi'an 710068, China

Multiplemyeloma (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.

图例: IGF1R是let-7b-5p的靶基因

Acta Biochim Biophys Sin (Shanghai). 2014 Nov;46(11):965-72. doi: 10.1093/abbs/gmu089

全文: http://abbs.oxfordjournals.org/content/46/11/965.full