AIM To uncover the role of hepatocyte nuclear factor 4 alpha(HNF4α) in regulating hepatic expression of micro RNAs.METHODS Microarray and real-time PCR were used to determine hepatic expression of micro RNAs in young...AIM To uncover the role of hepatocyte nuclear factor 4 alpha(HNF4α) in regulating hepatic expression of micro RNAs.METHODS Microarray and real-time PCR were used to determine hepatic expression of micro RNAs in young-adult mice lacking Hnf4α expression in liver(Hnf4α-Liv KO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-Ⅱ, and histone modifications to loci of micro RNAs in mouse liver and human hepatoma cells. Dual-luciferase reporter assay was conducted to determine effects of HNF4α on the promoters of mouse and human micro RNAs as well as effects of micro RNAs on the untranslated regions(3'UTR) of two genes in human hepatoma cells. RESULTS Microarray data indicated that most micro RNAs remained unaltered by Hnf4α deficiency in Hnf4α-Liv KO mice. However, certain liver-predominant micro RNAs were down-regulated similarly in young-adult male and female Hnf4α-Liv KO mice. The down-regulation of mi R-101, mi R-192, mi R-193 a, mi R-194, mi R-215, mi R-802, and mi R-122 as well as induction of mi R-34 and mi R-29 in male Hnf4α-Liv KO mice were confirmed by real-timePCR. Analysis of public chromatin immunoprecipitationsequencing data indicates that HNF4α directly binds to the promoters of mi R-101, mi R-122, mi R-194-2/mi R-192 and mi R-193, which is associated with histone marks of active transcription. Luciferase reporter assay showed that HNF4α markedly activated the promoters of mouse and human mi R-101b/mi R-101-2 and the mi R-194/mi R-192 cluster. Additionally, mi R-192 and mi R-194 significantly decreased activities of luciferase reporters for the 3'UTR of histone H3F3 and chromodomain helicase DNA binding protein 1(CHD1), respectively, suggesting that mi R-192 and mi R-194 might be important in chromosome remodeling through directly targeting H3F3 and CHD1.CONCLUSION HNF4α is essential for hepatic basal expression of a group of liver-enriched micro RNAs, including mi R-101, mi R-192, mi R-193 a, mi R-194 and mi R-802, through which HNF4α may play a major role in the post-transcriptional regulation of gene expression and maintenance of the epigenome in liver.展开更多
BACKGROUND Thyroid gland is an uncommon site for metastases from clear cell renal cell carcinoma(CCRCC)and literature is scarce.Due to the variable and often long lag time before development of metastases in patients ...BACKGROUND Thyroid gland is an uncommon site for metastases from clear cell renal cell carcinoma(CCRCC)and literature is scarce.Due to the variable and often long lag time before development of metastases in patients with CCRCC,thyroid nodules may be misdiagnosed initially as benign.This systematic review aims at a better understanding of the nature of these metastases.METHODS A bibliographic search was performed using PubMed(1990-2019),key words being“renal cell carcinoma,thyroid,kidney cancer,clear cell.”147 cases were analyzed.The patient’s characteristics assessed were:age,sex,stage,size of metastases,lag time,diagnostic modality,initial symptoms,treatment and outcome in last documented follow up.Binary logistic regression,Spearman’s rho and ANOVA were used to identify differences between the existing variables.RESULTS The mean age(±SD)was 64±(10)years in males and 64(±11)in females.The mean lag time to diagnosis of thyroid metastases was 8.7(±6.3)years.Gender distribution of the patients was 46.3%male,52.4%female.There was a weak correlation between lag time and size of metastases,not statistically significant.Size of metastases was significantly higher in symptomatic patients(6.06±3.51 cm)compared to those with painless mass(4.6±0.29 cm)and asymptomatic ones(3.93±1.99 cm)(P=0.03).Fine Needle Aspiration was diagnostic in 29.4%of cases,47.1%were non diagnostic.Most patients(80.3%)underwent thyroid surgery.At 1 year follow up,55.6%of patients operated were alive versus 35.3%who did not have surgery,though this was not statistically significant(P=0.1).CONCLUSION A larger size of thyroid metastasis was more likely to present with symptomatology.A high index of suspicion is warranted when evaluating thyroid nodules in CCRCC patients.There was no significant difference in outcome between patients who underwent surgery and those who did not.With the wider use of immune check-point inhibitors and tyrosine kinase inhibitors in metastatic CCRCC,surgery may eventually be reserved only for palliative purposes.展开更多
摩洛哥王国（Royaume du Maroc）位于非洲西北端的阿拉伯马格里布地区,东、南部与阿尔及利亚接壤,南部为摩实际占领的西撒哈拉地区,再往南是毛里塔尼亚,西濒大西洋,北临地中海,北隔直布罗陀海峡与西班牙相望。1月平均气温12℃,7月22℃-2...摩洛哥王国（Royaume du Maroc）位于非洲西北端的阿拉伯马格里布地区,东、南部与阿尔及利亚接壤,南部为摩实际占领的西撒哈拉地区,再往南是毛里塔尼亚,西濒大西洋,北临地中海,北隔直布罗陀海峡与西班牙相望。1月平均气温12℃,7月22℃-28℃。展开更多
文摘AIM To uncover the role of hepatocyte nuclear factor 4 alpha(HNF4α) in regulating hepatic expression of micro RNAs.METHODS Microarray and real-time PCR were used to determine hepatic expression of micro RNAs in young-adult mice lacking Hnf4α expression in liver(Hnf4α-Liv KO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-Ⅱ, and histone modifications to loci of micro RNAs in mouse liver and human hepatoma cells. Dual-luciferase reporter assay was conducted to determine effects of HNF4α on the promoters of mouse and human micro RNAs as well as effects of micro RNAs on the untranslated regions(3'UTR) of two genes in human hepatoma cells. RESULTS Microarray data indicated that most micro RNAs remained unaltered by Hnf4α deficiency in Hnf4α-Liv KO mice. However, certain liver-predominant micro RNAs were down-regulated similarly in young-adult male and female Hnf4α-Liv KO mice. The down-regulation of mi R-101, mi R-192, mi R-193 a, mi R-194, mi R-215, mi R-802, and mi R-122 as well as induction of mi R-34 and mi R-29 in male Hnf4α-Liv KO mice were confirmed by real-timePCR. Analysis of public chromatin immunoprecipitationsequencing data indicates that HNF4α directly binds to the promoters of mi R-101, mi R-122, mi R-194-2/mi R-192 and mi R-193, which is associated with histone marks of active transcription. Luciferase reporter assay showed that HNF4α markedly activated the promoters of mouse and human mi R-101b/mi R-101-2 and the mi R-194/mi R-192 cluster. Additionally, mi R-192 and mi R-194 significantly decreased activities of luciferase reporters for the 3'UTR of histone H3F3 and chromodomain helicase DNA binding protein 1(CHD1), respectively, suggesting that mi R-192 and mi R-194 might be important in chromosome remodeling through directly targeting H3F3 and CHD1.CONCLUSION HNF4α is essential for hepatic basal expression of a group of liver-enriched micro RNAs, including mi R-101, mi R-192, mi R-193 a, mi R-194 and mi R-802, through which HNF4α may play a major role in the post-transcriptional regulation of gene expression and maintenance of the epigenome in liver.
文摘BACKGROUND Thyroid gland is an uncommon site for metastases from clear cell renal cell carcinoma(CCRCC)and literature is scarce.Due to the variable and often long lag time before development of metastases in patients with CCRCC,thyroid nodules may be misdiagnosed initially as benign.This systematic review aims at a better understanding of the nature of these metastases.METHODS A bibliographic search was performed using PubMed(1990-2019),key words being“renal cell carcinoma,thyroid,kidney cancer,clear cell.”147 cases were analyzed.The patient’s characteristics assessed were:age,sex,stage,size of metastases,lag time,diagnostic modality,initial symptoms,treatment and outcome in last documented follow up.Binary logistic regression,Spearman’s rho and ANOVA were used to identify differences between the existing variables.RESULTS The mean age(±SD)was 64±(10)years in males and 64(±11)in females.The mean lag time to diagnosis of thyroid metastases was 8.7(±6.3)years.Gender distribution of the patients was 46.3%male,52.4%female.There was a weak correlation between lag time and size of metastases,not statistically significant.Size of metastases was significantly higher in symptomatic patients(6.06±3.51 cm)compared to those with painless mass(4.6±0.29 cm)and asymptomatic ones(3.93±1.99 cm)(P=0.03).Fine Needle Aspiration was diagnostic in 29.4%of cases,47.1%were non diagnostic.Most patients(80.3%)underwent thyroid surgery.At 1 year follow up,55.6%of patients operated were alive versus 35.3%who did not have surgery,though this was not statistically significant(P=0.1).CONCLUSION A larger size of thyroid metastasis was more likely to present with symptomatology.A high index of suspicion is warranted when evaluating thyroid nodules in CCRCC patients.There was no significant difference in outcome between patients who underwent surgery and those who did not.With the wider use of immune check-point inhibitors and tyrosine kinase inhibitors in metastatic CCRCC,surgery may eventually be reserved only for palliative purposes.
