The miRNA let-7a1 inhibits the expression of insulin-like growth factor 1 receptor (IGF1R) in prostate cancer PC-3 cells

• Published in: Asian journal of andrology Vol. 15; no. 6; pp. 753 - 758
• Main Authors: Wang, Li-Na, Chen, Wei-Wen, Zhang, Ju, Li, Chao-Yang, Liu, Chun-Yan, Xue, Jing, Zhang, Peng-Ju, Jiang, An-Li
• Format: Journal Article
• Language: English
• Published: China Medknow Publications & Media Pvt. Ltd 01.11.2013; Nature Publishing Group
• Subjects: 3' Untranslated Regions; Base Sequence; Cell Line, Tumor; DNA Primers; Humans; Male; MicroRNAs - genetics; Original; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Real-Time Polymerase Chain Reaction; Receptor, IGF Type 1 - genetics; RNA, Messenger - genetics
• DOI: 10.1038/aja.2013.84
• ISSN: 1008-682X; 1745-7262

Reduced microRNA (miRNA) let-7a expression and the activation of insulin-like growth factor-1 receptor (IGF1R) signalling are both involved in prostate cancer and progression. In the present study, we demonstrated that the growth inhibitory effect of let-7a1 is directly related to targeting IGF1R gene expression in PC-3 cells. TargetScan predicted three potential target sites (T1, T2 and T3) of let-7a in the 3' untranslational region (3' UTR) of IGF1R mRNA. Real-time PCR, Western blot and luciferase reporter assays were used to detect the effects of let-7a1 overexpression or let-7a1 inhibitor on the IGF1R gene expression in PC-3 cells. The results indicated that let-7a1 could inhibit IGF1R expression by directly targeting the T1 and T2 sites in the 3' UTR of the IGF1R mRNA. We then used RT-PCR, luciferase reporter assays, 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry and Hoechst 33342 staining to examine whether let-7a1-mediated inhibition of IGF1R expression also affects the IGF1R-mediated signalling events, including Elk1 activity and c-fos gene expression, proliferation, apoptosis and cell cycle. We demonstrated that let-7a1-mediated IGF1R downregulation was accompanied by attenuation of Elk1 activity and c-fos expression, inhibition of cell proliferation, enhanced apoptosis and cell cycle arrest, and that loss function of let-7a1 via inhibition can upregulate IGF1R accompanied by an increase of Elk1 activity and c-fos expression, thereby enhancing cell proliferation. Altogether, these findings suggest that let-7a may be novel therapeutic candidate for prostate cancer.