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
Background:MicroRNAs(miRNAs)are endogenous non-coding RNAS that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases.Overexpressed miRNAs play an important ro...Background:MicroRNAs(miRNAs)are endogenous non-coding RNAS that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases.Overexpressed miRNAs play an important role in amyotrophic lateral sclerosis(ALS);however,the pathogenic mechanisms of deregulated miRNAS are still unclear.Methods:We aimed to assess the dysfunction of RNAS or miRNAs in fALS(SOD1 mutations).We compared the RNA-seq of subcellular fractions in NSC-34 WT(hSOD1)and MT(hSOD1(G93A))cells to find altered RNAs or miRNAs.We identified that Hif1a and Mef2c were upregulated,and Mctp1 and Rarb were downregulated in the cytoplasm of NSC-34 MT cells.Results:SOD1 mutations decreased the level of miR-18b-5p.Induced Hif1a which is the target for miR-18b increased Mef2c expression as a transcription factor.Mef2c upregulated miR-206 as a transcription factor.Inhibition of Mctp1 and Rarb,which are targets of miR-206,induced intracellular Ca^2+ levels and reduced cell differentiation,respectively.The miR-18b-5p pathway was also observed in G93A Tg mice,fALS(G86S)patient,and iPSC-derived motor neurons from fALS(G17S)patient.Conclusions:Our data indicate that SOD1 mutation decreases miR-18b-5p,which sequentially regulates Hif1a,Mef2c,miR-206,Mctp1 and Rarb in fALS-linked SOD1 mutation.These results provide new insights into the downregulation of miR-18b-5p-dependent pathogenic mechanisms of ALS.展开更多
This paper gives a necessary condition for a kind of weakly invertible, invertible, weak inverse or inverse finite automata by linear RaRb transformation sequence. For such finite automata the existence of terminating...This paper gives a necessary condition for a kind of weakly invertible, invertible, weak inverse or inverse finite automata by linear RaRb transformation sequence. For such finite automata the existence of terminating RaRb transformation sequence is also established.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.
基金This research was supported by the Brain Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(2017M3C7A102536521 and 2018R1A5A202596413).
文摘Background:MicroRNAs(miRNAs)are endogenous non-coding RNAS that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases.Overexpressed miRNAs play an important role in amyotrophic lateral sclerosis(ALS);however,the pathogenic mechanisms of deregulated miRNAS are still unclear.Methods:We aimed to assess the dysfunction of RNAS or miRNAs in fALS(SOD1 mutations).We compared the RNA-seq of subcellular fractions in NSC-34 WT(hSOD1)and MT(hSOD1(G93A))cells to find altered RNAs or miRNAs.We identified that Hif1a and Mef2c were upregulated,and Mctp1 and Rarb were downregulated in the cytoplasm of NSC-34 MT cells.Results:SOD1 mutations decreased the level of miR-18b-5p.Induced Hif1a which is the target for miR-18b increased Mef2c expression as a transcription factor.Mef2c upregulated miR-206 as a transcription factor.Inhibition of Mctp1 and Rarb,which are targets of miR-206,induced intracellular Ca^2+ levels and reduced cell differentiation,respectively.The miR-18b-5p pathway was also observed in G93A Tg mice,fALS(G86S)patient,and iPSC-derived motor neurons from fALS(G17S)patient.Conclusions:Our data indicate that SOD1 mutation decreases miR-18b-5p,which sequentially regulates Hif1a,Mef2c,miR-206,Mctp1 and Rarb in fALS-linked SOD1 mutation.These results provide new insights into the downregulation of miR-18b-5p-dependent pathogenic mechanisms of ALS.
基金Project supported by the National Natural Science Foundation of China.
文摘This paper gives a necessary condition for a kind of weakly invertible, invertible, weak inverse or inverse finite automata by linear RaRb transformation sequence. For such finite automata the existence of terminating RaRb transformation sequence is also established.
