miR-181c/d is dysregulated in gastric cancer(GC).We investigated the amplification and expression of miR-181c/d and its predicted target genes in GC.Amplification of miR-181c/d was quantified by genomic real-time PCR ...miR-181c/d is dysregulated in gastric cancer(GC).We investigated the amplification and expression of miR-181c/d and its predicted target genes in GC.Amplification of miR-181c/d was quantified by genomic real-time PCR in GC and adjacent normal tissues,as well as the levels of mature miR-181c/d was performed by real-time PCR in the same tissues.The potential target genes of miR-181c/d were predicted using bioinformatics software.Expression of one potential target gene,PDCD4,was measured by semiquantitative RT-PCR,real-time PCR,and immunohistochemistry.Next,the relationship between miR181c/d expression and PDCD4 expression was analyzed.Results indicated that the amplification and expression of miR-181c/d were significantly higher in GC than in adjacent normal tissues(primary miR-181c/d,P\0.001;miR-181c,P=0.0344;miR-181d,P=0.0153),and there was a strong correlation between mature miR-181c/d and primary miR-181c/d.Thirty-two target genes were predicted,including PDCD4 which is a known tumor suppressor gene.Expression of PDCD4 was significantly down-regulated in GC as compared to adjacent normal tissues and was inversely correlated with miR-181c/d expression in GC(miR-181c and PDCD4:R=-0.496,P=0.008;miR-181d and PDCD4:R=-0.454,P=0.003).Therefore,miR-181c/d may play a pivotal role in the pathogenesis of GC by downregulating PDCD4 expression.展开更多
Programmed cell death 4 （PDCD4） is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer （CRC）. During CRC carcinogenesis, PDCD4 protein levels remarkably decrease...Programmed cell death 4 （PDCD4） is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer （CRC）. During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and conse- quently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken toge- ther, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.展开更多
基金supported by the National Basic Research Program(2012CB934002,2010CB912802)the National High Technology Research and Development Program(2012AA02A504,SS2012AA02A209,SS2012AA020821,and SS2012AA02A203)
文摘miR-181c/d is dysregulated in gastric cancer(GC).We investigated the amplification and expression of miR-181c/d and its predicted target genes in GC.Amplification of miR-181c/d was quantified by genomic real-time PCR in GC and adjacent normal tissues,as well as the levels of mature miR-181c/d was performed by real-time PCR in the same tissues.The potential target genes of miR-181c/d were predicted using bioinformatics software.Expression of one potential target gene,PDCD4,was measured by semiquantitative RT-PCR,real-time PCR,and immunohistochemistry.Next,the relationship between miR181c/d expression and PDCD4 expression was analyzed.Results indicated that the amplification and expression of miR-181c/d were significantly higher in GC than in adjacent normal tissues(primary miR-181c/d,P\0.001;miR-181c,P=0.0344;miR-181d,P=0.0153),and there was a strong correlation between mature miR-181c/d and primary miR-181c/d.Thirty-two target genes were predicted,including PDCD4 which is a known tumor suppressor gene.Expression of PDCD4 was significantly down-regulated in GC as compared to adjacent normal tissues and was inversely correlated with miR-181c/d expression in GC(miR-181c and PDCD4:R=-0.496,P=0.008;miR-181d and PDCD4:R=-0.454,P=0.003).Therefore,miR-181c/d may play a pivotal role in the pathogenesis of GC by downregulating PDCD4 expression.
文摘Programmed cell death 4 （PDCD4） is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer （CRC）. During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and conse- quently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken toge- ther, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.
