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Nam Keun Kim - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the Association Between MicroRNA Biogenesis Gene Polymorphisms and Venous Thromboembolism in Koreans
International journal of molecular sciences, 2019Co-Authors: Eo Jin Kim, Jung Oh Kim, Jung Hoon Sung, Han Sung Park, Chang Soo Ryu, So Young Chong, Nam Keun KimAbstract:Venous thromboembolism (VTE) involves the formation of a blood clot, typically in the deep veins of the leg or arm (deep vein thrombosis), which then travels via the circulatory system and ultimately lodges in the lungs, resulting in pulmonary embolism. A number of microRNAs (miRNAs) are well-known regulators of thrombosis and thrombolysis, and mutations in miRNA biogenesis genes, such as DICER1, DROSHA have been implicated in miRNA synthesis and function. We investigated the genetic association between polymorphisms in four miRNA biogenesis genes, DICER1 rs3742330A > G, DROSHA rs10719T > C, RAN rs14035C > T and XPO5 rs11077A > C, and VTE in 503 Koreans: 300 controls and 203 patients. Genotyping was assessed with polymerase chain reaction-restriction fragment length polymorphism assays. We detected associations between polymorphisms in RAN and XPO5 and VTE prevalence (RAN rs14035CC + CT versus TT: p = 0.018; XPO5 rs11077AA + AC versus CC: p C, polymorphism was associated with increased disease prevalence (TT versus TC + CC: p < 0.039). Our study demonstrates that RAN and XPO5 polymorphisms are associated with risk for VTE in Korean subjects.
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Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma.
PloS one, 2016Co-Authors: Mi Na Kim, Jung Oh Kim, Seungmin Lee, Hana Park, Ju Ho Lee, Kyu Sung Rim, Seong Gyu Hwang, Nam Keun KimAbstract:Single-nucleotide polymorphisms (SNPs) in microRNA machinery genes might affect microRNA processing and subsequently impact tumorigenesis. The aim of this study was to investigate the associations between SNPs in microRNA machinery genes and hepatocellular carcinoma (HCC) in a Korean population. Genotyping of six SNPs in microRNA machinery genes was performed using blood samples from 147 patients with HCC and 209 healthy control subjects. None of the six SNPs in microRNA machinery genes were significantly associated with HCC development. However, among the models for six polymorphic loci-DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) and XPO5 (rs11077)-one allele combination (A-A-T-C-C-C) showed synergistic effects in terms of an increased risk of HCC development (odds ratio = 8.881, 95% confidence interval [CI] = 1.889-41.750; P = 0.002). Multivariate Cox proportional hazard regression analysis showed a significant survival benefit for the DICER rs3742330 GG compared with the AA type (hazard ratio [HR], 0.314; 95% CI, 0.135-0.730; P = 0.007) and for the RAN rs14035 CT compared with the CC genotype (HR, 0.587; 95% CI, 0.349-0.987; P = 0.044). Although we found no direct association between DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) or XPO5 (rs11077) polymorphisms and HCC risk, we demonstrated that DICER (rs3742330) and RAN (rs14035) were associated with the survival of HCC patients. Future studies with larger samples are needed to determine associations of SNPs in microRNA machinery genes with HCC risk and prognosis.
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3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.
PloS one, 2015Co-Authors: Sung Hwan Cho, Young Joo Jeon, Jung Oh Kim, Jung Ki Yoo, Jong Woo Kim, Nam Keun KimAbstract:MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and XPO5 rs11077 AA genotype (CT/AA) carriers experienced reduced CRC susceptibility (both colon and rectal). Subgroup analysis demonstrated that the combined RAN rs14035 CT + TT genotype was associated with rectal cancer, but not colon cancer. In addition, the DICER1 rs3742330 AG genotype was associated with a significantly increased risk of colon cancer. Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer. In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate. Furthermore, patients diagnosed with hypertension or DM who carried the DROSHA rs10719 CC genotype showed increased CRC risk, while the XPO5 rs11077 AC+CC genotype led to increased CRC risk in patients with hypertension only. Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.
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Genetic variants in microRNA machinery genes are associate with idiopathic recurrent pregnancy loss risk
PLoS ONE, 2014Co-Authors: Yong Wook Jung, Hyung Chul Rah, Ji Hyang Kim, Sun Hee Cha, Ji Eun Shin, Young Joo Jeon, Dong-hee Choi, Nam Keun KimAbstract:OBJECTIVE: Key molecules involved in microRNA (miRNA) biogenesis, such as DROSHA, XPO5, and DICER, have been identified in trophoblast cells, confirming that the miRNA biogenesis pathway is active in human placenta. In addition, miRNAs regulate uterine gene expression associated with inflammatory responses during the peri-implantation period and participate in maternal-fetal immune tolerance. The purpose of this study was to demonstrate whether genetic polymorphisms in miRNA machinery genes show an association with idiopathic recurrent pregnancy loss (RPL) in Korean women.\n\nSTUDY DESIGN: We performed a case-control study with 238 controls and 338 women who had experienced at least two consecutive pregnancy losses between 1999 and 2010. Genotypes of miRNA machinery genes, including DICER rs3742330, DROSHA rs10719, RAN GTPase (RAN) rs14035, and exportin-5 (XPO5) rs11077 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The logistic odds ratios (ORs) of RPL were estimated with a 95% confidence interval (CI) in multivariate analysis after maternal age adjustment. Gene-gene interactions among the loci of the four gene polymorphisms were evaluated using the multifactor dimensionality reduction (MDR) method.\n\nRESULTS: The RAN rs14035 CC genotype and DICER rs3742330/DROSHA rs10719 GG/TC+CC, rs3742330/RAN rs14035 GG/CC, and DICER rs3742330/XPO5 rs11077 GG/AC+CC combinations were significantly associated with increased RPL risk, whereas the RAN rs14035 CT, DICER rs3742330/RAN rs14035 AA+AG/CT+TT, DROSHA rs10719/RAN rs14035 TC+CC/CT+TT, and RAN rs14035/XPO5 rs11077 CT+TT/AA combinations reduced RPL risk. The A-T-T-C and G-C-T-A allele combinations (DICER/DROSHA/RAN/XPO5) were 20 times more frequent in the RPL group than in the control group.\n\nCONCLUSION: Our study demonstrates the relationship between RPL development and the polymorphism of the miRNA machinery gene RAN and combined genotype of DROSHA/DICER.
Zhanjun Guo - One of the best experts on this subject based on the ideXlab platform.
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Single-nucleotide polymorphisms of microRNA processing machinery genes and risk of colorectal cancer.
OncoTargets and therapy, 2015Co-Authors: Yufei Zhao, Shengnan Zhao, Zhanjun GuoAbstract:Objective MicroRNA (miRNA)-related single-nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes can affect cancer risk, treatment efficacy, and patient prognosis. We genotyped 6 miR-SNPs of miRNA processing machinery genes including XPO5 (rs11077), RAN (rs14035), Dicer (rs3742330), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348) in a case-control study to evaluate their impact on colorectal cancer (CRC) risk.
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A miR-SNP of the XPO5 gene is associated with advanced non-small-cell lung cancer.
OncoTargets and therapy, 2013Co-Authors: Cuimin Ding, Hongjing Wang, Zhanjun GuoAbstract:Objectives MicroRNA (miRNA)-related single-nucleotide polymorphisms (SNPs) in miRNA processing machinery genes can affect cancer risk, treatment efficacy, and patient prognosis. A miR-SNP of rs11077 located in the 3′ untranslated region (3′ UTR) of the miRNA processing machinery gene XPO5 was examined in 112 advanced non-small-cell lung cancer (NSCLC) patients to evaluate its association with cancer outcome.
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A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients.
Biomedical reports, 2013Co-Authors: Zhanjun Guo, Hongjing Wang, Cuimin DingAbstract:MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes affect cancer risk, treatment efficacy and patient prognosis. A miR-SNP of rs11077 located in the 3′UTR of miRNA processing machinery gene XPO5 was examined in small cell lung cancer (SCLC) patients to evaluate its association with cancer survival. A total of 42 patients were enrolled in the present study and genotyped for rs11077 and survival was assessed using the Kaplan-Meier method, as well as univariate and multivariate analyses. The AA genotype of rs11077 was identified for its significant association with better survival time (P=0.023). In addition, rs11077 was found to associate independently with overall survival in SCLC patients by multivariate analysis (relative risk 2.469; 95% CI, 1.088–5.603; P=0.031). The findings of this study suggest that although miR-SNP studies for miRNA processing machinery genes are still at an early age, miR-SNPs have an impact on cancer survival. In conclusion, a miR-SNP in the 3′UTR region of the XPO5 gene was identified as an independent prognostic marker for survival of advanced SCLC patients.
J.p. Szaflik - One of the best experts on this subject based on the ideXlab platform.
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the analysis of single nucleotide polymorphisms of the dgcr8 and XPO5 genes and their association with the incidence of primary open angle glaucoma
Klinika oczna, 2017Co-Authors: Milena Molasy, J.p. Szaflik, Anna Walczak, K. Szymanek, Karolina Przybylowskasygut, Ireneusz MajsterekAbstract:Purpose To analyse the single nucleotide polymorphisms of DGCR8 and XPO5 genes, involved in miRNA processing pathway, in relation to the incidence of primary open-angle glaucoma. Material and methods Blood samples as the biological material used for the experiment were voluntarily donated by patients with known primary open-angle glaucoma and age-matched healthy controls. The two control groups – rs3757 DGCR8 and rs11077 XPO5 – consisted of 135 and 140 volunteers, respectively. The two study groups – rs3757 DGCR8 and rs11077 XPO5 – consisted of 137 and 138 subjects, respectively. The polymorphic variant frequencies of rs3757 and rs1107 were determined using DNA isolated from the peripheral blood lymphocytes in TaqMan® SNP Genotyping Assays. Results The statistical analysis revealed that the genotype AG of DGCR8 rs3757 occurred more frequently in healthy individuals (P = 0.001), while homozygote GG was present mostly in people affected by primary open-angle glaucoma (P = 0.003). No association between the risk of primary open angle glaucoma and AC/CC genotypes of XPO5 was found. Conclusions Many reports suggest the association between the miRNA alteration and the pathogenesis of glaucoma. The single nucleotide polymorphisms in DGCR8 and XPO5 genes, involved in microRNA biogenesis, may be the key factor in this process. Our experiment showed that genotype AG in rs3757 DGCR8 exhibits protective effect, decreasing the risk of primary open angle glaucoma, while the homozygote GG is probably associated with increased risk of glaucoma. The analysis of polymorphic variants of the genes involved in miRNA biogenesis could enable identification of glaucoma high-risk groups.
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The analysis of single nucleotide polymorphisms of the DGCR8 and XPO5 genes, and their association with the incidence of primary open angle glaucoma.
Klinika oczna, 2016Co-Authors: Milena Molasy, J.p. Szaflik, Anna Walczak, K. Szymanek, Karolina Przybyłowska-sygut, Ireneusz MajsterekAbstract:To analyse the single nucleotide polymorphisms of DGCR8 and XPO5 genes, involved in miRNA processing pathway, in relation to the incidence of primary open-angle glaucoma. Blood samples as the biological material used for the experiment were voluntarily donated by patients with known primary open-angle glaucoma and age-matched healthy controls. The two control groups – rs3757 DGCR8 and rs11077 XPO5 – consisted of 135 and 140 volunteers, respectively. The two study groups – rs3757 DGCR8 and rs11077 XPO5 – consisted of 137 and 138 subjects, respectively. The polymorphic variant frequencies of rs3757 and rs1107 were determined using DNA isolated from the peripheral blood lymphocytes in TaqMan® SNP Genotyping Assays. The statistical analysis revealed that the genotype AG of DGCR8 rs3757 occurred more frequently in healthy individuals (P = 0.001), while homozygote GG was present mostly in people affected by primary open-angle glaucoma (P = 0.003). No association between the risk of primary open angle glaucoma and AC/CC genotypes of XPO5 was found. Many reports suggest the association between the miRNA alteration and the pathogenesis of glaucoma. The single nucleotide polymorphisms in DGCR8 and XPO5 genes, involved in microRNA biogenesis, may be the key factor in this process. Our experiment showed that genotype AG in rs3757 DGCR8 exhibits protective effect, decreasing the risk of primary open angle glaucoma, while the homozygote GG is probably associated with increased risk of glaucoma. The analysis of polymorphic variants of the genes involved in miRNA biogenesis could enable identification of glaucoma high-risk groups.
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Association of microRNA DGCR8 and XPO5 gene polymorphisms with the risk of primary open angle glaucoma occurrence
Acta Ophthalmologica, 2015Co-Authors: Ireneusz Majsterek, Milena Molasy, Anna Walczak, Karolina Przybylowska-sygut, K. Szymanek, J.p. SzaflikAbstract:Purpose Many reports suggest the correlation between altered microRNA level and the pathogenesis of glaucoma. It is suspected that disruption in microRNA processing machinery may influence microRNAs action. The single nucleotide polymorphisms in genes DGCR8 and XPO5, which are involved in microRNA biogenesis may be the key factor in this process. Methods The blood samples of 80 patients affected by primary open angle glaucoma and 250 age matched controls were enrolled to this study. The DNA was isolated from the peripheral blood lymphocytes. The polymorphic variant frequencies of DGCR8 (rs 3757) and XPO5 (rs 1107) genes were determined using TaqMan® SNP Genotyping Assays. Results The statistical analysis revealed that the polymorphism of DGCR8 gene did not affect to the risk of primary open angle glaucoma. While, the TT genotype of XPO5 was found to be present mainly in patients not affected by glaucoma (P=0.049746). Conclusions In conclusion, it was evaluated that the TT genotype of XPO5 gene might have protective effect on the risk of primary open angle glaucoma. Therefore, future analysis of polymorphic variants of genes involved in microRNA biogenesis could be used for patient's diagnosis according to glaucoma occurence.
Yong Gao - One of the best experts on this subject based on the ideXlab platform.
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Downregulation and tumor-suppressive role of XPO5 in hepatocellular carcinoma.
Molecular and cellular biochemistry, 2016Co-Authors: Xiao Wang, Hui Cai, Yong GaoAbstract:XPO5 (Exp5, Exportin-5) is a transporter protein mainly mediating pre-microRNAs' nuclear export. Recent studies have demonstrated that XPO5 may play crucial roles in a few of cancers. However, little is known about XPO5 in hepatocellular carcinoma (HCC). In the present study, we elucidated the expression of XPO5 by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining in HCC samples and conducted several functional analyses to address its effects on HCC development. The results demonstrated that both mRNA and protein levels of XPO5 were downregulated in HCC tissues compared to adjacent non-cancerous livers. Ectopic expression of XPO5 significantly suppressed cell proliferation, colony formation, growth in soft agar, and tumorigenicity in nude mice, whereas knockdown of XPO5 by RNA inference showed opposite phenotypes. Moreover, XPO5 knockdown promoted HCC cell migration and decreased the expression of E-cadherin and p53. Additionally, after treatment with DAC and TSA, the mRNA level of XPO5 was upregulated in HCC cells tested, implicating that epigenetic modulation may be involved in the transcription of XPO5. Collectively, our findings suggest that XPO5 functions as a potential tumor suppressor in the development and progression of HCC as well as a promising molecular target for HCC therapy.
Cuimin Ding - One of the best experts on this subject based on the ideXlab platform.
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A miR-SNP of the XPO5 gene is associated with advanced non-small-cell lung cancer.
OncoTargets and therapy, 2013Co-Authors: Cuimin Ding, Hongjing Wang, Zhanjun GuoAbstract:Objectives MicroRNA (miRNA)-related single-nucleotide polymorphisms (SNPs) in miRNA processing machinery genes can affect cancer risk, treatment efficacy, and patient prognosis. A miR-SNP of rs11077 located in the 3′ untranslated region (3′ UTR) of the miRNA processing machinery gene XPO5 was examined in 112 advanced non-small-cell lung cancer (NSCLC) patients to evaluate its association with cancer outcome.
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A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients.
Biomedical reports, 2013Co-Authors: Zhanjun Guo, Hongjing Wang, Cuimin DingAbstract:MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes affect cancer risk, treatment efficacy and patient prognosis. A miR-SNP of rs11077 located in the 3′UTR of miRNA processing machinery gene XPO5 was examined in small cell lung cancer (SCLC) patients to evaluate its association with cancer survival. A total of 42 patients were enrolled in the present study and genotyped for rs11077 and survival was assessed using the Kaplan-Meier method, as well as univariate and multivariate analyses. The AA genotype of rs11077 was identified for its significant association with better survival time (P=0.023). In addition, rs11077 was found to associate independently with overall survival in SCLC patients by multivariate analysis (relative risk 2.469; 95% CI, 1.088–5.603; P=0.031). The findings of this study suggest that although miR-SNP studies for miRNA processing machinery genes are still at an early age, miR-SNPs have an impact on cancer survival. In conclusion, a miR-SNP in the 3′UTR region of the XPO5 gene was identified as an independent prognostic marker for survival of advanced SCLC patients.
