BACKGROUND:A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations,which promote tumor progression. Epigenetic abnormalities include changes in DNA methyl...BACKGROUND:A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations,which promote tumor progression. Epigenetic abnormalities include changes in DNA methylation and in the modification of histones.This study aimed to assess the status of methylation in the CpG island(CGI)of the tumor necrosis factor receptor superfamily member 10c(TNFRSF10C) with combined bisulfite restriction analysis(COBRA)and to evaluate its role in the progression of pancreatic cancer(PC). METHODS:The methylation status of four PC cell lines was assessed using COBRA and/or bisulfite genomic sequencing (BGS).Changes in methylation and TNFRSF10C expression in PC cell lines before and after treatment with 5-aza-2’-deoxycytidine(5-aza-dC)and/or trichostatin A(TSA)were assessed by BGS and real-time RT-PCR.Apoptosis in the four cell lines was tested by flow cytometry(FCM)and TUNEL assay. RESULTS:The methylation status of the TNFRSF10C promoter was assessed in PC cells(BxPC-3:68.84±8.71%;CFPAC-1:0; PANC-1:96.77±4.57%;SW1990:54.97±7.33%)with the COBRA assay,which was confirmed by the results of BGS.After treatment with 5-aza-dC and/or TSA,apoptosis was induced in PC cells to different degrees,and the levels of TNFRSF10C transcriptional expression in the PC cell lines(except CFPAC-1) increased markedly after 5-aza-dC treatment. CONCLUSIONS:A high frequency of CGI methylation in the TNFRSF10C promoter results in inactivation of the gene and enhancement of tumor growth in most PC cell lines(except CFPAC-1).Inactivation of TNFRSF10C by CGI hypermethylation can play an important role in PC progression and be potentially useful as a diagnostic marker and a new therapeutic approach for PC.展开更多
BACKGROUND Recent studies have emphasized the emerging importance of long noncoding RNAs(lncRNAs)in colorectal cancer(CRC).However,the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully...BACKGROUND Recent studies have emphasized the emerging importance of long noncoding RNAs(lncRNAs)in colorectal cancer(CRC).However,the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated.AIM To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC.METHODS TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC,and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed.The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in vivo.Mechanistically,we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA.RESULTS TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients.A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation,migration ability and invasion ability of colon cancer cells in vitro and in vivo.A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression,ultimately promoting colorectal tumorigenesis and progression.CONCLUSION TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC,indicating that it may be a novel target for CRC therapy.展开更多
基金supported by a grant from the National Natural Science Foundation of China(30471691)
文摘BACKGROUND:A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations,which promote tumor progression. Epigenetic abnormalities include changes in DNA methylation and in the modification of histones.This study aimed to assess the status of methylation in the CpG island(CGI)of the tumor necrosis factor receptor superfamily member 10c(TNFRSF10C) with combined bisulfite restriction analysis(COBRA)and to evaluate its role in the progression of pancreatic cancer(PC). METHODS:The methylation status of four PC cell lines was assessed using COBRA and/or bisulfite genomic sequencing (BGS).Changes in methylation and TNFRSF10C expression in PC cell lines before and after treatment with 5-aza-2’-deoxycytidine(5-aza-dC)and/or trichostatin A(TSA)were assessed by BGS and real-time RT-PCR.Apoptosis in the four cell lines was tested by flow cytometry(FCM)and TUNEL assay. RESULTS:The methylation status of the TNFRSF10C promoter was assessed in PC cells(BxPC-3:68.84±8.71%;CFPAC-1:0; PANC-1:96.77±4.57%;SW1990:54.97±7.33%)with the COBRA assay,which was confirmed by the results of BGS.After treatment with 5-aza-dC and/or TSA,apoptosis was induced in PC cells to different degrees,and the levels of TNFRSF10C transcriptional expression in the PC cell lines(except CFPAC-1) increased markedly after 5-aza-dC treatment. CONCLUSIONS:A high frequency of CGI methylation in the TNFRSF10C promoter results in inactivation of the gene and enhancement of tumor growth in most PC cell lines(except CFPAC-1).Inactivation of TNFRSF10C by CGI hypermethylation can play an important role in PC progression and be potentially useful as a diagnostic marker and a new therapeutic approach for PC.
基金The study was reviewed and approved by the Ethics Committee of the Second Hospital of Hebei Medical University(No.2021-R241).
文摘BACKGROUND Recent studies have emphasized the emerging importance of long noncoding RNAs(lncRNAs)in colorectal cancer(CRC).However,the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated.AIM To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC.METHODS TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC,and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed.The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in vivo.Mechanistically,we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA.RESULTS TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients.A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation,migration ability and invasion ability of colon cancer cells in vitro and in vivo.A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression,ultimately promoting colorectal tumorigenesis and progression.CONCLUSION TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC,indicating that it may be a novel target for CRC therapy.
