RESUMO
Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. TDRD1, a germ cell-specific gene, is erroneously expressed in more than half of prostate tumors, but its role in prostate cancer development remains elusive. In this study, we identified a PRMT5-TDRD1 signaling axis that regulates the proliferation of prostate cancer cells. PRMT5 is a protein arginine methyltransferase essential for small nuclear ribonucleoprotein (snRNP) biogenesis. Methylation of Sm proteins by PRMT5 is a critical initiation step for assembling snRNPs in the cytoplasm, and the final snRNP assembly takes place in Cajal bodies in the nucleus. By mass spectrum analysis, we found that TDRD1 interacts with multiple subunits of the snRNP biogenesis machinery. In the cytoplasm, TDRD1 interacts with methylated Sm proteins in a PRMT5-dependent manner. In the nucleus, TDRD1 interacts with Coilin, the scaffold protein of Cajal bodies. Ablation of TDRD1 in prostate cancer cells disrupted the integrity of Cajal bodies, affected the snRNP biogenesis, and reduced cell proliferation. Taken together, this study represents the first characterization of TDRD1 functions in prostate cancer development and suggests TDRD1 as a potential therapeutic target for prostate cancer treatment.
Assuntos
Neoplasias da Próstata , Ribonucleoproteínas Nucleares Pequenas , Masculino , Humanos , Ribonucleoproteínas Nucleares Pequenas/genética , Ribonucleoproteínas Nucleares Pequenas/análise , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Testículo/metabolismo , Núcleo Celular/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proliferação de Células/genética , Células HeLa , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMO
Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. TDRD1, a germ cell-specific gene, is erroneously expressed in more than half of prostate tumors, but its role in prostate cancer development remains elusive. In this study, we identified a PRMT5-TDRD1 signaling axis that regulates the proliferation of prostate cancer cells. PRMT5 is a protein arginine methyltransferase essential for small nuclear ribonucleoprotein (snRNP) biogenesis. Methylation of Sm proteins by PRMT5 is a critical initiation step for assembling snRNPs in the cytoplasm, and the final snRNP assembly takes place in Cajal bodies in the nucleus. By mass spectrum analysis, we found that TDRD1 interacts with multiple subunits of the snRNP biogenesis machinery. In the cytoplasm, TDRD1 interacts with methylated Sm proteins in a PRMT5-dependent manner. In the nucleus, TDRD1 interacts with Coilin, the scaffold protein of Cajal bodies. Ablation of TDRD1 in prostate cancer cells disrupted the integrity of Cajal bodies, affected the snRNP biogenesis, and reduced cell proliferation. Taken together, this study represents the first characterization of TDRD1 functions in prostate cancer development and suggests TDRD1 as a potential therapeutic target for prostate cancer treatment.
RESUMO
BACKGROUND: Extracts of Vernonia amygdalina (V. amygdalina) have been shown to affect the serum lipid profile of some laboratory animals in previous studies. Its impact on serum lipid profile and the histological changes in atherosclerosis has not been studied. Our aim was to determine the effects of V. amygdalina on atherosclerotic lesions induced in rabbits on high-cholesterol diet. METHODS: 18 male rabbits were randomly divided into three groups of control, atherogenic diet, and atherogenic diet + 200 mg/kg of V. amygdalina. The rabbits were fed a normal diet (control group) or a diet supplemented by 0.5% cholesterol and 1% methionine (second and third groups, respectively) for 12 weeks. The fasting sera of all animals were collected at baseline and at the end of the 12 weeks, to determine the levels of lipid profile and the aortas underwent pathomorphological examination. RESULTS: The two groups on the atherogenic diet had significantly increased serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the control group. The serum triglyceride (TG) was not statistically different in all three groups. High-density lipoprotein cholesterol (HDL-C) was significantly increased in the V. amygdalina group, compared to the control group but there was no statistically significant difference between the two groups on atherogenic diet. The two groups of rabbits that were on high-cholesterol diet (atherogenic diet group, as well as the atherogenic diet + 200 mg/kg of V. amygdalina) developed histological evidence of atherosclerosis. However, there was no histological difference between the lesions observed in these two groups. CONCLUSION: The use of 200 mg/kg of aqueous extract of V. amygdalina in rabbits did not appear to exert a significant effect on the serum lipid profile. It also did not appear to have any beneficial effect on the development of atherosclerotic lesions.
