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A unique computational approach was undertaken to identify targets of miR-17-3p that impart an oncogenic potential to the cells of the prostate. Utilizing this approach, we identified insulin growth factor receptor 1 (IGF1R) as a potential target of miR-17-3p. IGF1R imparts an oncogenic approach to the cells by helping cells escape apoptosis, become hypertrophic and increase the production of extracellular proteases that allow cells to detach from neighbors. The regulation of insulin growth factor receptor 1 by human microRNA-17-3p was evaluated using a western blot analysis of prostate cancer cell lines. Protein levels were compared in a cell line that expressed a non-targeting control RNA and a cell line that expressed microRNA-17-3p. The cell line that expressed the non-targeting control had significantly higher levels of IGF1R protein than the cell line expressing more of the active microRNA. Based on this experiment, it appears that microRNA-17-3p might regulate the insulin growth factor receptor 1.

Darbo tikslas: Ištirti insulino augimo faktoriaus (IGF – 1) geno poveikį galvijų produktyvumo savybėms. Darbo uždaviniai: 1. Surinkti ir išanalizuoti mokslinę literatūrą apie insulino augimo faktoriaus (IGF – 1) geną ir jo įtaką galvijų produktyvumo savybėms. 2. Nustatyti insulino augimo faktoriaus (IGF – 1) geno alelių ir genotipų dažnius. 3. Įvertinti insulino augimo faktoriaus (IGF – 1) geno įtaką galvijų priesvoriui. Pirmą kartą Lietuvoje buvo ištirtas insulino augimo faktoriaus (IGF – 1) genas bei nustatyta jo įtaka galvijų priesvoriui. Darbo praktinė reikšmė: Rastas insulino augimo faktoriaus (IGF – 1) geno polimorfizmas bei nustatyta jo įtaka galvijų priesvoriui leidžia atrinkti gyvulius su pageidaujamu genotipu ir tokiu būdu, vykdant selekciją genetinių žymenų pagalba, gerinti galvijų priesvorį. Išvados: 1. Tirtoje galvijų grupėje insulino augimo faktoriaus (IGF – 1) geno rasti du aleliai – A ir B. A alelis rastas 0,471 dažniu, o B alelis, didinantis galvijų priesvorį, rastas 0,529 dažniu. 2. Didžiausiu dažniu B alelis rastas Limuzinų galvijų veislėje (0,711). 3. Tirtoje galvijų grupėje insulino augimo faktoriaus (IGF – 1) geno rasti trys AA, AB ir BB genotipai. AA genotipą turėjo 24,0 proc. galvijų, AB genotipą turėjo 47,0 proc. galvijų, o BB genotipą, kuris didina galvijų priesvorį, turėjo 29,0 proc. galvijų. 4. Didžiausią kiekį, net 47 proc., BB genotipą turėjo Limuzinų veislės galvijai. 5. BB genotipo galvijai statistiškai reikšmingai turėjo didesnį priesvorį (86... [toliau žr. visą tekstą] / Object and tasks of work: Collect and analyze scientific literature on IGF – 1 gene and examine its effect on cattle production traits. Estimate genotype distribution and allelic frequencies at the IGF – 1 gene. Examine the effect of IGF – 1 gene on weight gain in cattle. Research methodology: Analysis of scientific literature, scientific articles, and statistical data. The practice part involved research of cattle IGF – 1 gene. Research findings and results were discussed using method of generalization. Theoretical analysis used scientific papers by different foreign and Lithuanian researchers. Different articles and research material offering information on the issue under consideration were used as the basis for the research. Results and conclusions. The IGF – 1 gene located on chromosome 5 was found to be a factor that regulates growth rate in cattle. Our research found that IGF – 1 gene has two alleles – A and B. Allele A frequency was 0.471, and allele B – 0.529. Allele A at its highest frequency of 0.708 was found in Lithuanian Black and White cattle breed, and allele B at its highest frequency of 0.711 – in Limousin cattle breed (see Table 2). The following three different genotypes were found for IGF – 1 gene: AA, AB, and BB. AA genotype of IGF – 1 gene showed the lowest frequency and varied from 0.053 in Limousin cattle breed to 0.500 in Lithuanian Black and White cattle breed, whereas AB genotype showed its highest frequency and varied from 0.400 in Lithuanian Red... [to full text]

Context: Non-alcoholic fatty liver disease (NAFLD) is known to be associated with insulin resistance, atherosclerosis, and low serum IGF-I levels. We have described a large cohort of patients with isolated GH deficiency (IGHD) due to the c.57+1G&#8594;A mutation in the GHRH receptor gene. These subjects have increased insulin sensitivity (IS), delayed atherosclerosis, and normal longevity. We hypothesized that despite visceral obesity NAFLD would be absent or mild due to the increased IS. Objective: To assess the prevalence and severity of NAFLD in adult subjects with lifetime, congenital, untreated IGHD. Methods: We studied 22 IGHD adults and 25 controls (CO) matched for age and gender. NAFLD was assessed by a comprehensive liver function panel, and ultrasonographic pattern (HP) coded as 0=absent; 1=mild; 2=moderate; and 3=severe. Results: Compared to CO, IGHD individual had lower serum IGF-I (p<0.0001), higher total cholesterol (p=0.027), lower prothrombin time (p=0.017), similar activated partial thromboplastin time and fibrinogen values. ALT values were similar in the two groups, but AST was higher in IGHD (p=0.013). However, more IGHD subjects (7/22) than CO (3/23) had ALT above the upper limit of normal (p=0.044). The prevalence of NAFLD was higher in IGHD than CO (61% vs. 29%, p=0.032), and the HP score was higher in IGHD than CO (p=0.041), but severe NAFLD was not observed in any IGHD (or CO) individual. Conclusions: liver HP score is increased in lifetime untreated congenital IGHD, but the increase in transaminases is mild, suggesting lack of advanced forms of NAFLD. / Introdução: A doença hepática gordurosa não alcoólica (DHGNA) é conhecida por ser associada à resistência insulínica, aterosclerose e baixos níveis de IGF-I. Descrevemos uma coorte com deficiência isolada de GH (DIGH) devido à mutação c.57+1G&#8594;A no gene do receptor do hormônio liberador do GHRH com obesidade visceral, sensibilidade à insulina aumentada, com aterosclerose tardia e longevidade normal. Método: Estudamos 22 adultos com DIGH e 25 controles (CO), pareados por idade e gênero. A DHGNA foi avaliada por um painel abrangente da função hepática e um padrão ultrassonográfico hiperecogênico (PH), codificado como 0 = ausente; 1 = leve; 2 = moderada; e 3 = grave. Resultados: Em comparação com controle, indivíduos com DHGNA apresentaram concentrações menores de IGF - I (p < 0,0001), maior colesterol total (p = 0,027), reduzido tempo de protrombina (p = 0,017), e valores semelhantes de tempo de tromboplastina parcial ativado e do fibrinogênio. Os valores da ALT foram semelhantes em ambos os grupos, mas os da AST foram maiores nos indivíduos com DIGH (p = 0,013). No entanto, o numero de indivíduos com ALT acima do limite superior da normalidade foi maior no grupo DIGH (7 / 22) de que no CO (3/23), (p = 0,044). A frequência de DHGNA foi mais alta na DIGH que no CO (61 x 29 %, p = 0.032) e PH foi superior em DIGH do que nos CO (p = 0,041), mas não foi observada DHGNA grave em qualquer indivíduo com DIGH (ou CO). Conclusão: O escore do PH é maior nos indivíduos com DIGH não tratada. No entanto, o aumento da AST é moderado, sugerindo ausência de formas avançadas de DHGNA na DIGH.

Context: Non-alcoholic fatty liver disease (NAFLD) is known to be associated with insulin resistance, atherosclerosis, and low serum IGF-I levels. We have described a large cohort of patients with isolated GH deficiency (IGHD) due to the c.57+1G→A mutation in the GHRH receptor gene. These subjects have increased insulin sensitivity (IS), delayed atherosclerosis, and normal longevity. We hypothesized that despite visceral obesity NAFLD would be absent or mild due to the increased IS. Objective: To assess the prevalence and severity of NAFLD in adult subjects with lifetime, congenital, untreated IGHD. Methods: We studied 22 IGHD adults and 25 controls (CO) matched for age and gender. NAFLD was assessed by a comprehensive liver function panel, and ultrasonographic pattern (HP) coded as 0=absent; 1=mild; 2=moderate; and 3=severe. Results: Compared to CO, IGHD individual had lower serum IGF-I (p<0.0001), higher total cholesterol (p=0.027), lower prothrombin time (p=0.017), similar activated partial thromboplastin time and fibrinogen values. ALT values were similar in the two groups, but AST was higher in IGHD (p=0.013). However, more IGHD subjects (7/22) than CO (3/23) had ALT above the upper limit of normal (p=0.044). The prevalence of NAFLD was higher in IGHD than CO (61% vs. 29%, p=0.032), and the HP score was higher in IGHD than CO (p=0.041), but severe NAFLD was not observed in any IGHD (or CO) individual. Conclusions: liver HP score is increased in lifetime untreated congenital IGHD, but the increase in transaminases is mild, suggesting lack of advanced forms of NAFLD. / Introdução: A doença hepática gordurosa não alcoólica (DHGNA) é conhecida por ser associada à resistência insulínica, aterosclerose e baixos níveis de IGF-I. Descrevemos uma coorte com deficiência isolada de GH (DIGH) devido à mutação c.57+1G→A no gene do receptor do hormônio liberador do GHRH com obesidade visceral, sensibilidade à insulina aumentada, com aterosclerose tardia e longevidade normal. Método: Estudamos 22 adultos com DIGH e 25 controles (CO), pareados por idade e gênero. A DHGNA foi avaliada por um painel abrangente da função hepática e um padrão ultrassonográfico hiperecogênico (PH), codificado como 0 = ausente; 1 = leve; 2 = moderada; e 3 = grave. Resultados: Em comparação com controle, indivíduos com DHGNA apresentaram concentrações menores de IGF - I (p < 0,0001), maior colesterol total (p = 0,027), reduzido tempo de protrombina (p = 0,017), e valores semelhantes de tempo de tromboplastina parcial ativado e do fibrinogênio. Os valores da ALT foram semelhantes em ambos os grupos, mas os da AST foram maiores nos indivíduos com DIGH (p = 0,013). No entanto, o numero de indivíduos com ALT acima do limite superior da normalidade foi maior no grupo DIGH (7 / 22) de que no CO (3/23), (p = 0,044). A frequência de DHGNA foi mais alta na DIGH que no CO (61 x 29 %, p = 0.032) e PH foi superior em DIGH do que nos CO (p = 0,041), mas não foi observada DHGNA grave em qualquer indivíduo com DIGH (ou CO). Conclusão: O escore do PH é maior nos indivíduos com DIGH não tratada. No entanto, o aumento da AST é moderado, sugerindo ausência de formas avançadas de DHGNA na DIGH.