title: The miRNA let-7a1 inhibits the expression of insulin-like growth factor 1 receptor (IGF1R) in prostate cancer PC-3 cells.
abstract: 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.
authors: Li-Na
authors: LN
authors: Wang
authors: Wei-Wen
authors: WW
authors: Chen
authors: Ju
authors: J
authors: Zhang
authors: Chao-Yang
authors: CY
authors: Li
authors: Chun-Yan
authors: CY
authors: Liu
authors: Jing
authors: J
authors: Xue
authors: Peng-Ju
authors: PJ
authors: Zhang
authors: An-Li
authors: AL
authors: Jiang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D017931:DNA Primers; D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; D017526:Receptor, IGF Type 1
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