Objective: The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB...Objective: The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB) and p16 among benign prostatic hyperplasia (BPH) and prostate cancer patients. Methods: In this case-control study, 63 patients were included in three groups; 21 with BPH as the control group, 21 with prostate cancer and good prognostic factors (based on prostate-specific antigen, Gleason score and stage) as good prognosis group, and 21 with prostate cancer and poor prognostic features as poor prognosis group. The prostate biopsy specimen of each individual was examined for hypermethylation of RARB and p16 promoters by methylation specific PCR (MSPCR). Results: Seven (33.3%) patients with good prognosis and 15 (71.4%) patients with poor prognosis were positive for RARB methylation, which were significantly higher than controls (P <0.0001). p16 promoter methylation was shown in 19.0% and 47.6% patients with good and poor prognosis, respectively. The RARB and p16 promoter methylation in the poor prognosis group was significantly higher than that in the good prognosis group (P =0.02 for RARB and P<0.0001 for p16). Conclusion: Hypermethylation of RARB and p16 promoters may predict prognosis in prostate cancer.展开更多
Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical...Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.展开更多
Some adult vertebrate species,such as newts,axolotls and zebrafish,have the ability to regenerate their central nervous system(CNS).However,the factors that establish a permissive CNS environment for correct morphol...Some adult vertebrate species,such as newts,axolotls and zebrafish,have the ability to regenerate their central nervous system(CNS).However,the factors that establish a permissive CNS environment for correct morphological and functional regeneration in these species are not well understood.Recent evidence supports a role for retinoid signaling in the intrinsic ability of neurons,in these regeneration-competent species,to regrow after CNS injury.Previously,we demonstrated that a specific retinoic acid receptor(RAR)subtype,RARβ,mediates the effects of endogenous retinoic acid(RA)on neuronal growth and guidance in the adult newt CNS after injury.Here,we now examine the expression of the retinoid X receptor RXRα(a potential heterodimeric transcriptional regulator with RARβ),in newt tail and spinal cord regeneration.We show that at 21 days post-amputation(dpa),RXRαis expressed at temporally distinct periods and in non-overlapping spatial domains compared to RARβ.Whereas RARβprotein levels increase,RXRαproteins level decrease by 21 dpa.A selective agonist for RXR,SR11237,prevents both this downregulation of RXRαand upregulation of RARβand inhibits tail and caudal spinal cord regeneration.Moreover,treatment with a selective antagonist for RARβ,LE135,inhibits regeneration with the same morphological consequences as treatment with SR11237.Interestingly,LE135 treatment also inhibits the normal downregulation of RXRαin tail and spinal cord tissues at 21 dpa.These results reveal a previously unidentified,indirect regulatory feedback loop between these two receptor subtypes in regulating the regeneration of tail and spinal cord tissues in this regeneration-competent newt.展开更多
The thymine DNA glycosylase (TDG) is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair (BER) of G:T and G:U DNA mismatches arising from the deamination of...The thymine DNA glycosylase (TDG) is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair (BER) of G:T and G:U DNA mismatches arising from the deamination of 5-methyl cytosine (5-MeC) and cytosine,respectively.Recent studies have pointed at a role of TDG during the active demethylation of 5-MeC within CpG islands.TDG interacts with the histone acetylase CREB-binding protein (CBP) to activate CBP-dependent transcription.In addition,TDG also interacts with the retinoic acid receptor α (RARα),resulting in the activation of RARα target genes.Here we provide evidence for the existence of a functional ternary complex containing TDG,CBP and activated RARα.Using global transcriptome profiling,we uncover a coupling of de novo methylation-sensitive and RA-dependent transcription,which coincides with a significant subset of CBP target genes.The introduction of a point mutation in TDG,which neither affects overall protein structure nor BER activity,leads to a significant loss in ternary complex stability,resulting in the deregulation of RA targets involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling of TDG's epigenomic and transcription regulatory function through ternary complexes with CBP and RARα.展开更多
To determine the mechanism of all trans retinoic acid (ATRA) on growth inhibition in human gastric cancer cells Methods Gastric cancer cell lines: MGC80 3, BGC 823, SGC 7901 and MKN 45 CAT assay, Northern blo...To determine the mechanism of all trans retinoic acid (ATRA) on growth inhibition in human gastric cancer cells Methods Gastric cancer cell lines: MGC80 3, BGC 823, SGC 7901 and MKN 45 CAT assay, Northern blot, Western blot, gene transfection and MTT assay Results ATRA can inhibit the activator protein 1 (AP 1) activity in ATRA sensitive cell lines, but not in ATRA resistant cell line, and the anti AP 1 activity of ATRA is mediated by its receptor, retinoic acid receptor α (RARα) ATRA can also inhibit the expression of cJun and cFos One of the mechanisms for ATRA to inhibit the growth of gastric cancer cells may be through its inhibitory effect on the AP 1 activity and its influence on up regulation of RARα expression The inhibition of cJun and cFos expressions by ATRA may also contribute to the anti AP 1 activity Conclusions ATRA inhibits the growth of gastric cancer cells through the regulation of AP 1 activity This action is mediated by RARα展开更多
Multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE),a pathologically similar disease used to model MS in rodents,are typical CD4^(^(+))T cell-dominated autoimmune diseases.CD4^(+)interleukin(IL)17...Multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE),a pathologically similar disease used to model MS in rodents,are typical CD4^(^(+))T cell-dominated autoimmune diseases.CD4^(+)interleukin(IL)17^(+)T cells(Th17 cells)have been well studied and have shown that they play a critical role in the pathogenesis of MS/EAE.However,studies have suggested that CD8^(+)IL17^(+)T cells(Tc17 cells)have a similar phenotype and cytokine and transcription factor profiles to those of Th17 cells and have been found to be crucial in the pathogenesis of autoimmune diseases,including MS/EAE,psoriasis,type I diabetes,rheumatoid arthritis,and systemic lupus erythematosus.However,the evidence for this is indirect and insufficient.Therefore,we searched for related publications and attempted to summarize the current knowledge on the role of Tc17 cells in the pathogenesis of MS/EAE,as well as in the pathogenesis of other autoimmune diseases,and to find out whether Tc17 cells or Th17 cells play a more critical role in autoimmune disease,especially in MS and EAE pathogenesis,or whether the interaction between these two cell types plays a critical role in the development of the disease.展开更多
文摘Objective: The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB) and p16 among benign prostatic hyperplasia (BPH) and prostate cancer patients. Methods: In this case-control study, 63 patients were included in three groups; 21 with BPH as the control group, 21 with prostate cancer and good prognostic factors (based on prostate-specific antigen, Gleason score and stage) as good prognosis group, and 21 with prostate cancer and poor prognostic features as poor prognosis group. The prostate biopsy specimen of each individual was examined for hypermethylation of RARB and p16 promoters by methylation specific PCR (MSPCR). Results: Seven (33.3%) patients with good prognosis and 15 (71.4%) patients with poor prognosis were positive for RARB methylation, which were significantly higher than controls (P <0.0001). p16 promoter methylation was shown in 19.0% and 47.6% patients with good and poor prognosis, respectively. The RARB and p16 promoter methylation in the poor prognosis group was significantly higher than that in the good prognosis group (P =0.02 for RARB and P<0.0001 for p16). Conclusion: Hypermethylation of RARB and p16 promoters may predict prognosis in prostate cancer.
文摘Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.
基金supported by Natural Sciences and Engineering Council of Canada Discovery Grant to RLC and GES
文摘Some adult vertebrate species,such as newts,axolotls and zebrafish,have the ability to regenerate their central nervous system(CNS).However,the factors that establish a permissive CNS environment for correct morphological and functional regeneration in these species are not well understood.Recent evidence supports a role for retinoid signaling in the intrinsic ability of neurons,in these regeneration-competent species,to regrow after CNS injury.Previously,we demonstrated that a specific retinoic acid receptor(RAR)subtype,RARβ,mediates the effects of endogenous retinoic acid(RA)on neuronal growth and guidance in the adult newt CNS after injury.Here,we now examine the expression of the retinoid X receptor RXRα(a potential heterodimeric transcriptional regulator with RARβ),in newt tail and spinal cord regeneration.We show that at 21 days post-amputation(dpa),RXRαis expressed at temporally distinct periods and in non-overlapping spatial domains compared to RARβ.Whereas RARβprotein levels increase,RXRαproteins level decrease by 21 dpa.A selective agonist for RXR,SR11237,prevents both this downregulation of RXRαand upregulation of RARβand inhibits tail and caudal spinal cord regeneration.Moreover,treatment with a selective antagonist for RARβ,LE135,inhibits regeneration with the same morphological consequences as treatment with SR11237.Interestingly,LE135 treatment also inhibits the normal downregulation of RXRαin tail and spinal cord tissues at 21 dpa.These results reveal a previously unidentified,indirect regulatory feedback loop between these two receptor subtypes in regulating the regeneration of tail and spinal cord tissues in this regeneration-competent newt.
基金funded by the Centre National de la Recherche Scientifique(CNRS)and the Genopole Evry
文摘The thymine DNA glycosylase (TDG) is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair (BER) of G:T and G:U DNA mismatches arising from the deamination of 5-methyl cytosine (5-MeC) and cytosine,respectively.Recent studies have pointed at a role of TDG during the active demethylation of 5-MeC within CpG islands.TDG interacts with the histone acetylase CREB-binding protein (CBP) to activate CBP-dependent transcription.In addition,TDG also interacts with the retinoic acid receptor α (RARα),resulting in the activation of RARα target genes.Here we provide evidence for the existence of a functional ternary complex containing TDG,CBP and activated RARα.Using global transcriptome profiling,we uncover a coupling of de novo methylation-sensitive and RA-dependent transcription,which coincides with a significant subset of CBP target genes.The introduction of a point mutation in TDG,which neither affects overall protein structure nor BER activity,leads to a significant loss in ternary complex stability,resulting in the deregulation of RA targets involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling of TDG's epigenomic and transcription regulatory function through ternary complexes with CBP and RARα.
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 39880 0 1 5 )andtheNationalOutstandingYouthScienceFoun
文摘To determine the mechanism of all trans retinoic acid (ATRA) on growth inhibition in human gastric cancer cells Methods Gastric cancer cell lines: MGC80 3, BGC 823, SGC 7901 and MKN 45 CAT assay, Northern blot, Western blot, gene transfection and MTT assay Results ATRA can inhibit the activator protein 1 (AP 1) activity in ATRA sensitive cell lines, but not in ATRA resistant cell line, and the anti AP 1 activity of ATRA is mediated by its receptor, retinoic acid receptor α (RARα) ATRA can also inhibit the expression of cJun and cFos One of the mechanisms for ATRA to inhibit the growth of gastric cancer cells may be through its inhibitory effect on the AP 1 activity and its influence on up regulation of RARα expression The inhibition of cJun and cFos expressions by ATRA may also contribute to the anti AP 1 activity Conclusions ATRA inhibits the growth of gastric cancer cells through the regulation of AP 1 activity This action is mediated by RARα
基金Fund for Creative Research Group of Affiliated First Hospital of Hunan Traditional Chinese Medical College, China(No. 2021B-003)Key Plans of Hunan Administration Traditional Chinese Medicine, China(No. 201915)+2 种基金Natural Science Foundation of Hunan Province, China(No. 2018JJ6043)Health and Family Planning Commission of Hunan Province, China(No. B20180815)Technology Plan Project of Zhuzhou City, Hunan Province, China(No. 2021-003)
文摘Multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE),a pathologically similar disease used to model MS in rodents,are typical CD4^(^(+))T cell-dominated autoimmune diseases.CD4^(+)interleukin(IL)17^(+)T cells(Th17 cells)have been well studied and have shown that they play a critical role in the pathogenesis of MS/EAE.However,studies have suggested that CD8^(+)IL17^(+)T cells(Tc17 cells)have a similar phenotype and cytokine and transcription factor profiles to those of Th17 cells and have been found to be crucial in the pathogenesis of autoimmune diseases,including MS/EAE,psoriasis,type I diabetes,rheumatoid arthritis,and systemic lupus erythematosus.However,the evidence for this is indirect and insufficient.Therefore,we searched for related publications and attempted to summarize the current knowledge on the role of Tc17 cells in the pathogenesis of MS/EAE,as well as in the pathogenesis of other autoimmune diseases,and to find out whether Tc17 cells or Th17 cells play a more critical role in autoimmune disease,especially in MS and EAE pathogenesis,or whether the interaction between these two cell types plays a critical role in the development of the disease.