Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma
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. Gen...
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| creator | Kim, Mi Na Kim, Jung Oh Lee, Seung Min Park, Hana Lee, Ju Ho Rim, Kyu Sung Hwang, Seong Gyu Kim, Nam Keun |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0162279 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0162279</identifier><identifier>PMID: 27611467</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Apoptosis ; Biology and life sciences ; Cancer genetics ; Carbon-carbon composites ; Carcinoma, Hepatocellular - genetics ; Care and treatment ; Case-Control Studies ; Colorectal cancer ; Confidence intervals ; DEAD-box RNA Helicases - genetics ; Development and progression ; Enzymes ; Esophagus ; Female ; Gene expression ; Genes ; Genetic aspects ; Genotyping ; Haplotypes ; Hepatocellular carcinoma ; Humans ; Internal medicine ; Karyopherins - genetics ; Life sciences ; Liver cancer ; Liver Neoplasms - genetics ; Machinery ; Machinery and equipment ; Male ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; Middle Aged ; miRNA ; Patient outcomes ; Patients ; Polymorphism, Single Nucleotide ; Prognosis ; ran GTP-Binding Protein - genetics ; Regression Analysis ; Republic of Korea ; Ribonuclease III - genetics ; Ribonucleic acid ; Risk ; RNA ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Statistical analysis ; Studies ; Survival ; Survival analysis ; Survivors ; Synergistic effect ; Synergistic effects ; Tumorigenesis</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0162279-e0162279</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Kim et al 2016 Kim et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-4caa5bebe5d236c894e055a06cd4186b1c7bfa5d2003d1baf741abd0c1eb47d03</citedby><cites>FETCH-LOGICAL-c725t-4caa5bebe5d236c894e055a06cd4186b1c7bfa5d2003d1baf741abd0c1eb47d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017754/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017754/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27611467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Mi Na</creatorcontrib><creatorcontrib>Kim, Jung Oh</creatorcontrib><creatorcontrib>Lee, Seung Min</creatorcontrib><creatorcontrib>Park, Hana</creatorcontrib><creatorcontrib>Lee, Ju Ho</creatorcontrib><creatorcontrib>Rim, Kyu Sung</creatorcontrib><creatorcontrib>Hwang, Seong Gyu</creatorcontrib><creatorcontrib>Kim, Nam Keun</creatorcontrib><title>Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Biology and life sciences</subject><subject>Cancer genetics</subject><subject>Carbon-carbon composites</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>Colorectal cancer</subject><subject>Confidence intervals</subject><subject>DEAD-box RNA Helicases - genetics</subject><subject>Development and progression</subject><subject>Enzymes</subject><subject>Esophagus</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genotyping</subject><subject>Haplotypes</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Internal medicine</subject><subject>Karyopherins - genetics</subject><subject>Life sciences</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Machinery</subject><subject>Machinery and equipment</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prognosis</subject><subject>ran GTP-Binding Protein - genetics</subject><subject>Regression Analysis</subject><subject>Republic of Korea</subject><subject>Ribonuclease III - genetics</subject><subject>Ribonucleic acid</subject><subject>Risk</subject><subject>RNA</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Survival</subject><subject>Survival analysis</subject><subject>Survivors</subject><subject>Synergistic effect</subject><subject>Synergistic effects</subject><subject>Tumorigenesis</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1Fv0zAUhSMEYmPwDxBEQkLw0GI7Tuy8TKoKbJUmhjbYq3Vj37QuaVzspMC_x6Hd1KI9TH6I5fudY-fYN0leUjKmmaAflq73LTTjtWtxTGjBmCgfJce0zNioYCR7vDc_Sp6FsCQkz2RRPE2OmCgo5YU4Tn7cgLfQWdemtk27BaYfrUafQmvSq8mX9AxbDOnEYzoJwemIokl_2W6RXvd-YzfQDLqv0QHbLmwr57iGzmlsmr4Bn07Ba9u6FTxPntTQBHyx-54k3z9_-jY9H11cns2mk4uRFizvRlwD5BVWmBuWFVqWHEmeAym04VQWFdWiqiEWCckMraAWnEJliKZYcWFIdpK83vquGxfULqegqKSS8BhJEYnZljAOlmrt7Qr8H-XAqn8Lzs8V-M7qBhWDPNdlVTNqKMe6rmSWS23AoBG1LPLodbrbra9WaHTMwUNzYHpYae1Czd1G5YQKkfNo8G5n4N3PHkOnVjYM6UGLrh_OzYSUrGTyASgtKcuYLCP65j_0_iB21Bziv9q2dvGIejBVEy5IySmXQ6Dje6g4DK6sju-vtnH9QPD-QBCZDn93c-hDULPrq4ezlzeH7Ns9doHQdIvgmn54v-EQ5FtQexeCx_ruPihRQ_vcpqGG9lG79omyV_t3eSe67ZfsL1euFXc</recordid><startdate>20160909</startdate><enddate>20160909</enddate><creator>Kim, Mi Na</creator><creator>Kim, Jung Oh</creator><creator>Lee, Seung Min</creator><creator>Park, Hana</creator><creator>Lee, Ju Ho</creator><creator>Rim, Kyu Sung</creator><creator>Hwang, Seong Gyu</creator><creator>Kim, Nam Keun</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160909</creationdate><title>Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma</title><author>Kim, Mi Na ; Kim, Jung Oh ; Lee, Seung Min ; Park, Hana ; Lee, Ju Ho ; Rim, Kyu Sung ; Hwang, Seong Gyu ; Kim, Nam Keun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-4caa5bebe5d236c894e055a06cd4186b1c7bfa5d2003d1baf741abd0c1eb47d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Analysis</topic><topic>Apoptosis</topic><topic>Biology and life sciences</topic><topic>Cancer genetics</topic><topic>Carbon-carbon composites</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>Colorectal cancer</topic><topic>Confidence intervals</topic><topic>DEAD-box RNA Helicases - genetics</topic><topic>Development and progression</topic><topic>Enzymes</topic><topic>Esophagus</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genotyping</topic><topic>Haplotypes</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Internal medicine</topic><topic>Karyopherins - genetics</topic><topic>Life sciences</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Machinery</topic><topic>Machinery and equipment</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prognosis</topic><topic>ran GTP-Binding Protein - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Mi Na</au><au>Kim, Jung Oh</au><au>Lee, Seung Min</au><au>Park, Hana</au><au>Lee, Ju Ho</au><au>Rim, Kyu Sung</au><au>Hwang, Seong Gyu</au><au>Kim, Nam Keun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-09-09</date><risdate>2016</risdate><volume>11</volume><issue>9</issue><spage>e0162279</spage><epage>e0162279</epage><pages>e0162279-e0162279</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27611467</pmid><doi>10.1371/journal.pone.0162279</doi><tpages>e0162279</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1818049326 |
| source | PubMed Central (Open access); MEDLINE; Public Library of Science; DOAJ Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Analysis Apoptosis Biology and life sciences Cancer genetics Carbon-carbon composites Carcinoma, Hepatocellular - genetics Care and treatment Case-Control Studies Colorectal cancer Confidence intervals DEAD-box RNA Helicases - genetics Development and progression Enzymes Esophagus Female Gene expression Genes Genetic aspects Genotyping Haplotypes Hepatocellular carcinoma Humans Internal medicine Karyopherins - genetics Life sciences Liver cancer Liver Neoplasms - genetics Machinery Machinery and equipment Male Medical prognosis Medicine Medicine and Health Sciences Metastasis MicroRNA MicroRNAs MicroRNAs - genetics Middle Aged miRNA Patient outcomes Patients Polymorphism, Single Nucleotide Prognosis ran GTP-Binding Protein - genetics Regression Analysis Republic of Korea Ribonuclease III - genetics Ribonucleic acid Risk RNA Single nucleotide polymorphisms Single-nucleotide polymorphism Statistical analysis Studies Survival Survival analysis Survivors Synergistic effect Synergistic effects Tumorigenesis |
| title | Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T17%3A00%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Variation%20in%20the%20Dicer%20and%20RAN%20Genes%20Are%20Associated%20with%20Survival%20in%20Patients%20with%20Hepatocellular%20Carcinoma&rft.jtitle=PloS%20one&rft.au=Kim,%20Mi%20Na&rft.date=2016-09-09&rft.volume=11&rft.issue=9&rft.spage=e0162279&rft.epage=e0162279&rft.pages=e0162279-e0162279&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0162279&rft_dat=%3Cgale_plos_%3EA470941480%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1818049326&rft_id=info:pmid/27611467&rft_galeid=A470941480&rft_doaj_id=oai_doaj_org_article_2a55c9bf21d14effb8358cdaded7f865&rfr_iscdi=true |