Reduced microRNA （miRNA） let-7a expression and the activation of insulin-like growth factor-1 receptor （IGFIR） signalling are both involved in prostate cancer and progression. In the present study, we demonstrated...Reduced microRNA （miRNA） let-7a expression and the activation of insulin-like growth factor-1 receptor （IGFIR） signalling are both involved in prostate cancer and progression. In the present study, we demonstrated that the growth inhibitory effect of let-7al is directly related to targeting IGFIRgene 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 IGFIR mRNA. Real-time PCR, Western blot and luciferase reporter assays were used to detect the effects of let-7al overexpression or let-7al inhibitor on the IGFIRgene expression in PC-3 cells. The results indicated that let-7al could inhibit IGFIR expression by directly targeting the T1 and T2 sites in the 3＇ UTR of the IGFIR 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-7al-mediated inhibition of IGFIR expression also affects the IGFIR-mediated signalling events, including Elk1 activity and c-fos gene expression, proliferation, apoptosis and cell cycle. We demonstrated that let-7al-mediated IGFIR 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-7al via inhibition can upregulate IGF1R accompanied by an increase of Elk1 activity and c-fos expression, thereby enhancing cell proliferation. Altogether, these findings sueeest that let-7a mav be novel therapeutic candidate for Drostate cancer.展开更多
The insulin-like growth factor 1（IGF1） gene is a member of the group of somatotropin axis genes that play a significant role in cell proliferation and growth of muscles. Here, we searched for polymorphisms in buffal...The insulin-like growth factor 1（IGF1） gene is a member of the group of somatotropin axis genes that play a significant role in cell proliferation and growth of muscles. Here, we searched for polymorphisms in buffalo IGF1 and found two novel single nucleotide polymorphisms（SNPs）, G64 A and G280A, in the noncoding sequences of exon 1 and exon 4, respectively. Statistical analysis of different genotypes showed that the individuals with GG genotypes had significantly（P〈0.05） higher body weight（BW） and average daily gain（ADG） than those with other genotypes at ages of 3–6 months in G64A SNP and 6–9 months in G280A SNP. The combined genotypes of these two SNPs produced three haplotypes, GG/GG, AG/AG, and AA/AA, which were significantly associated（P〈0.0001） with BW and ADG at an age from 3 to 12 months. Buffaloes with the homozygous GG/GG haplotype showed higher growth performance than other buffaloes. The two SNPs were correlated with m RNA levels of IGF1 and IGF1 receptor（IGF1 R） in semitendinosus muscle as well as with the serum concentration level of IGF1. Also, buffaloes with GG/GG haplotype showed higher m RNA and serum concentration levels. The data revealed that these two SNPs could be valuable genetic markers for selection of Egyptian buffaloes for better performance in the population.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China （Nos. 81071720 and 81172045）, Shandong Provincial Programs for Science and Technology Development （No. 2012GSF 11820） and Foundation for Outstanding Young Scientist in Shandong Province （No. 2006BS03066）.
文摘Reduced microRNA （miRNA） let-7a expression and the activation of insulin-like growth factor-1 receptor （IGFIR） signalling are both involved in prostate cancer and progression. In the present study, we demonstrated that the growth inhibitory effect of let-7al is directly related to targeting IGFIRgene 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 IGFIR mRNA. Real-time PCR, Western blot and luciferase reporter assays were used to detect the effects of let-7al overexpression or let-7al inhibitor on the IGFIRgene expression in PC-3 cells. The results indicated that let-7al could inhibit IGFIR expression by directly targeting the T1 and T2 sites in the 3＇ UTR of the IGFIR 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-7al-mediated inhibition of IGFIR expression also affects the IGFIR-mediated signalling events, including Elk1 activity and c-fos gene expression, proliferation, apoptosis and cell cycle. We demonstrated that let-7al-mediated IGFIR 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-7al via inhibition can upregulate IGF1R accompanied by an increase of Elk1 activity and c-fos expression, thereby enhancing cell proliferation. Altogether, these findings sueeest that let-7a mav be novel therapeutic candidate for Drostate cancer.
基金Project supported by the Science Technology Development Fund(STDF,No.2585),Ministry of Scientific Research,Egypt
文摘The insulin-like growth factor 1（IGF1） gene is a member of the group of somatotropin axis genes that play a significant role in cell proliferation and growth of muscles. Here, we searched for polymorphisms in buffalo IGF1 and found two novel single nucleotide polymorphisms（SNPs）, G64 A and G280A, in the noncoding sequences of exon 1 and exon 4, respectively. Statistical analysis of different genotypes showed that the individuals with GG genotypes had significantly（P〈0.05） higher body weight（BW） and average daily gain（ADG） than those with other genotypes at ages of 3–6 months in G64A SNP and 6–9 months in G280A SNP. The combined genotypes of these two SNPs produced three haplotypes, GG/GG, AG/AG, and AA/AA, which were significantly associated（P〈0.0001） with BW and ADG at an age from 3 to 12 months. Buffaloes with the homozygous GG/GG haplotype showed higher growth performance than other buffaloes. The two SNPs were correlated with m RNA levels of IGF1 and IGF1 receptor（IGF1 R） in semitendinosus muscle as well as with the serum concentration level of IGF1. Also, buffaloes with GG/GG haplotype showed higher m RNA and serum concentration levels. The data revealed that these two SNPs could be valuable genetic markers for selection of Egyptian buffaloes for better performance in the population.
