Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer
Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA m...
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| creator | Aoki, Hironori Yamamoto, Eiichiro Takasawa, Akira Niinuma, Takeshi Yamano, Hiro-O Harada, Taku Matsushita, Hiro-O Yoshikawa, Kenjiro Takagi, Ryo Harada, Eiji Tanaka, Yoshihito Yoshida, Yuko Aoyama, Tomoyuki Eizuka, Makoto Yorozu, Akira Kitajima, Hiroshi Kai, Masahiro Sawada, Norimasa Sugai, Tamotsu Nakase, Hiroshi Suzuki, Hiromu |
| description | Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by
mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including
, methylation of which progressively increased during the development of TSAs.
was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps (
< 0.001). RT-PCR and immunohistochemistry revealed that SMOC1 was expressed in normal colon and SSA/Ps, but its expression was decreased in TSAs. Ectopic expression of SMOC1 suppressed proliferation, colony formation and
tumor formation by CRC cells. Analysis of colorectal lesions (
= 847) revealed that
is frequently methylated in TSAs, high-grade adenomas and CRCs. Among these,
methylation was strongly associated with
mutation and CpG island methylator phenotype (CIMP)-low. These results demonstrate that epigenetic silencing of
is associated with TSA development but is rarely observed in SSA/Ps. SMOC1 expression could thus be a diagnostic marker of serrated lesions, and
methylation could play a role in neoplastic pathways in TSAs and conventional adenomas. |
| doi_str_mv | 10.18632/oncotarget.23523 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5797007</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2001912213</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-e6456f83d3400269136c5499a96d082a8341f5c946b6538232d879c47b2423b23</originalsourceid><addsrcrecordid>eNpVUctKBDEQDKKo6H6AF8nRy655z-QiyOILlD2snkM20zNGZpI1yQr-vYOur750Q1VXF10InVAyo7Xi7DwGF4tNHZQZ45LxHXRItdBTJiXf_TMfoEnOL2QsKaqa6X10wLTgknJ1iJZXa99BgOIdzr6H4HzocGzx8mExp9gHXJJtfPEx2B5nSMkWaLBtIMTBYhsa7GIfE7gy4s4GB-kY7bW2zzDZ9iP0dH31OL-d3i9u7uaX91PHpSpTUEKqtuYNF4QwpUc_TgqtrVYNqZmtuaCtdFqolZK8Zpw1daWdqFZMML5i_AhdfOmuN6sBGgdh9NqbdfKDTe8mWm_-I8E_my6-GVnpipBqFDjbCqT4uoFczOCzg763AeImG0YI1ZQxykcq_aK6FHNO0P6cocR85mF-8zCfeYw7p3_9_Wx8f59_AIohiKQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2001912213</pqid></control><display><type>article</type><title>Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>PubMed Central</source><source>Free E- Journals</source><creator>Aoki, Hironori ; Yamamoto, Eiichiro ; Takasawa, Akira ; Niinuma, Takeshi ; Yamano, Hiro-O ; Harada, Taku ; Matsushita, Hiro-O ; Yoshikawa, Kenjiro ; Takagi, Ryo ; Harada, Eiji ; Tanaka, Yoshihito ; Yoshida, Yuko ; Aoyama, Tomoyuki ; Eizuka, Makoto ; Yorozu, Akira ; Kitajima, Hiroshi ; Kai, Masahiro ; Sawada, Norimasa ; Sugai, Tamotsu ; Nakase, Hiroshi ; Suzuki, Hiromu</creator><creatorcontrib>Aoki, Hironori ; Yamamoto, Eiichiro ; Takasawa, Akira ; Niinuma, Takeshi ; Yamano, Hiro-O ; Harada, Taku ; Matsushita, Hiro-O ; Yoshikawa, Kenjiro ; Takagi, Ryo ; Harada, Eiji ; Tanaka, Yoshihito ; Yoshida, Yuko ; Aoyama, Tomoyuki ; Eizuka, Makoto ; Yorozu, Akira ; Kitajima, Hiroshi ; Kai, Masahiro ; Sawada, Norimasa ; Sugai, Tamotsu ; Nakase, Hiroshi ; Suzuki, Hiromu</creatorcontrib><description>Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by
mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including
, methylation of which progressively increased during the development of TSAs.
was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps (
< 0.001). RT-PCR and immunohistochemistry revealed that SMOC1 was expressed in normal colon and SSA/Ps, but its expression was decreased in TSAs. Ectopic expression of SMOC1 suppressed proliferation, colony formation and
tumor formation by CRC cells. Analysis of colorectal lesions (
= 847) revealed that
is frequently methylated in TSAs, high-grade adenomas and CRCs. Among these,
methylation was strongly associated with
mutation and CpG island methylator phenotype (CIMP)-low. These results demonstrate that epigenetic silencing of
is associated with TSA development but is rarely observed in SSA/Ps. SMOC1 expression could thus be a diagnostic marker of serrated lesions, and
methylation could play a role in neoplastic pathways in TSAs and conventional adenomas.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.23523</identifier><identifier>PMID: 29435136</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Research Paper</subject><ispartof>Oncotarget, 2018-01, Vol.9 (4), p.4707-4721</ispartof><rights>Copyright: © 2018 Aoki et al. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-e6456f83d3400269136c5499a96d082a8341f5c946b6538232d879c47b2423b23</citedby><cites>FETCH-LOGICAL-c356t-e6456f83d3400269136c5499a96d082a8341f5c946b6538232d879c47b2423b23</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/PMC5797007/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797007/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29435136$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aoki, Hironori</creatorcontrib><creatorcontrib>Yamamoto, Eiichiro</creatorcontrib><creatorcontrib>Takasawa, Akira</creatorcontrib><creatorcontrib>Niinuma, Takeshi</creatorcontrib><creatorcontrib>Yamano, Hiro-O</creatorcontrib><creatorcontrib>Harada, Taku</creatorcontrib><creatorcontrib>Matsushita, Hiro-O</creatorcontrib><creatorcontrib>Yoshikawa, Kenjiro</creatorcontrib><creatorcontrib>Takagi, Ryo</creatorcontrib><creatorcontrib>Harada, Eiji</creatorcontrib><creatorcontrib>Tanaka, Yoshihito</creatorcontrib><creatorcontrib>Yoshida, Yuko</creatorcontrib><creatorcontrib>Aoyama, Tomoyuki</creatorcontrib><creatorcontrib>Eizuka, Makoto</creatorcontrib><creatorcontrib>Yorozu, Akira</creatorcontrib><creatorcontrib>Kitajima, Hiroshi</creatorcontrib><creatorcontrib>Kai, Masahiro</creatorcontrib><creatorcontrib>Sawada, Norimasa</creatorcontrib><creatorcontrib>Sugai, Tamotsu</creatorcontrib><creatorcontrib>Nakase, Hiroshi</creatorcontrib><creatorcontrib>Suzuki, Hiromu</creatorcontrib><title>Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by
mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including
, methylation of which progressively increased during the development of TSAs.
was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps (
< 0.001). RT-PCR and immunohistochemistry revealed that SMOC1 was expressed in normal colon and SSA/Ps, but its expression was decreased in TSAs. Ectopic expression of SMOC1 suppressed proliferation, colony formation and
tumor formation by CRC cells. Analysis of colorectal lesions (
= 847) revealed that
is frequently methylated in TSAs, high-grade adenomas and CRCs. Among these,
methylation was strongly associated with
mutation and CpG island methylator phenotype (CIMP)-low. These results demonstrate that epigenetic silencing of
is associated with TSA development but is rarely observed in SSA/Ps. SMOC1 expression could thus be a diagnostic marker of serrated lesions, and
methylation could play a role in neoplastic pathways in TSAs and conventional adenomas.</description><subject>Research Paper</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpVUctKBDEQDKKo6H6AF8nRy655z-QiyOILlD2snkM20zNGZpI1yQr-vYOur750Q1VXF10InVAyo7Xi7DwGF4tNHZQZ45LxHXRItdBTJiXf_TMfoEnOL2QsKaqa6X10wLTgknJ1iJZXa99BgOIdzr6H4HzocGzx8mExp9gHXJJtfPEx2B5nSMkWaLBtIMTBYhsa7GIfE7gy4s4GB-kY7bW2zzDZ9iP0dH31OL-d3i9u7uaX91PHpSpTUEKqtuYNF4QwpUc_TgqtrVYNqZmtuaCtdFqolZK8Zpw1daWdqFZMML5i_AhdfOmuN6sBGgdh9NqbdfKDTe8mWm_-I8E_my6-GVnpipBqFDjbCqT4uoFczOCzg763AeImG0YI1ZQxykcq_aK6FHNO0P6cocR85mF-8zCfeYw7p3_9_Wx8f59_AIohiKQ</recordid><startdate>20180112</startdate><enddate>20180112</enddate><creator>Aoki, Hironori</creator><creator>Yamamoto, Eiichiro</creator><creator>Takasawa, Akira</creator><creator>Niinuma, Takeshi</creator><creator>Yamano, Hiro-O</creator><creator>Harada, Taku</creator><creator>Matsushita, Hiro-O</creator><creator>Yoshikawa, Kenjiro</creator><creator>Takagi, Ryo</creator><creator>Harada, Eiji</creator><creator>Tanaka, Yoshihito</creator><creator>Yoshida, Yuko</creator><creator>Aoyama, Tomoyuki</creator><creator>Eizuka, Makoto</creator><creator>Yorozu, Akira</creator><creator>Kitajima, Hiroshi</creator><creator>Kai, Masahiro</creator><creator>Sawada, Norimasa</creator><creator>Sugai, Tamotsu</creator><creator>Nakase, Hiroshi</creator><creator>Suzuki, Hiromu</creator><general>Impact Journals LLC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180112</creationdate><title>Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer</title><author>Aoki, Hironori ; Yamamoto, Eiichiro ; Takasawa, Akira ; Niinuma, Takeshi ; Yamano, Hiro-O ; Harada, Taku ; Matsushita, Hiro-O ; Yoshikawa, Kenjiro ; Takagi, Ryo ; Harada, Eiji ; Tanaka, Yoshihito ; Yoshida, Yuko ; Aoyama, Tomoyuki ; Eizuka, Makoto ; Yorozu, Akira ; Kitajima, Hiroshi ; Kai, Masahiro ; Sawada, Norimasa ; Sugai, Tamotsu ; Nakase, Hiroshi ; Suzuki, Hiromu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-e6456f83d3400269136c5499a96d082a8341f5c946b6538232d879c47b2423b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Research Paper</topic><toplevel>online_resources</toplevel><creatorcontrib>Aoki, Hironori</creatorcontrib><creatorcontrib>Yamamoto, Eiichiro</creatorcontrib><creatorcontrib>Takasawa, Akira</creatorcontrib><creatorcontrib>Niinuma, Takeshi</creatorcontrib><creatorcontrib>Yamano, Hiro-O</creatorcontrib><creatorcontrib>Harada, Taku</creatorcontrib><creatorcontrib>Matsushita, Hiro-O</creatorcontrib><creatorcontrib>Yoshikawa, Kenjiro</creatorcontrib><creatorcontrib>Takagi, Ryo</creatorcontrib><creatorcontrib>Harada, Eiji</creatorcontrib><creatorcontrib>Tanaka, Yoshihito</creatorcontrib><creatorcontrib>Yoshida, Yuko</creatorcontrib><creatorcontrib>Aoyama, Tomoyuki</creatorcontrib><creatorcontrib>Eizuka, Makoto</creatorcontrib><creatorcontrib>Yorozu, Akira</creatorcontrib><creatorcontrib>Kitajima, Hiroshi</creatorcontrib><creatorcontrib>Kai, Masahiro</creatorcontrib><creatorcontrib>Sawada, Norimasa</creatorcontrib><creatorcontrib>Sugai, Tamotsu</creatorcontrib><creatorcontrib>Nakase, Hiroshi</creatorcontrib><creatorcontrib>Suzuki, Hiromu</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aoki, Hironori</au><au>Yamamoto, Eiichiro</au><au>Takasawa, Akira</au><au>Niinuma, Takeshi</au><au>Yamano, Hiro-O</au><au>Harada, Taku</au><au>Matsushita, Hiro-O</au><au>Yoshikawa, Kenjiro</au><au>Takagi, Ryo</au><au>Harada, Eiji</au><au>Tanaka, Yoshihito</au><au>Yoshida, Yuko</au><au>Aoyama, Tomoyuki</au><au>Eizuka, Makoto</au><au>Yorozu, Akira</au><au>Kitajima, Hiroshi</au><au>Kai, Masahiro</au><au>Sawada, Norimasa</au><au>Sugai, Tamotsu</au><au>Nakase, Hiroshi</au><au>Suzuki, Hiromu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2018-01-12</date><risdate>2018</risdate><volume>9</volume><issue>4</issue><spage>4707</spage><epage>4721</epage><pages>4707-4721</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by
mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including
, methylation of which progressively increased during the development of TSAs.
was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps (
< 0.001). RT-PCR and immunohistochemistry revealed that SMOC1 was expressed in normal colon and SSA/Ps, but its expression was decreased in TSAs. Ectopic expression of SMOC1 suppressed proliferation, colony formation and
tumor formation by CRC cells. Analysis of colorectal lesions (
= 847) revealed that
is frequently methylated in TSAs, high-grade adenomas and CRCs. Among these,
methylation was strongly associated with
mutation and CpG island methylator phenotype (CIMP)-low. These results demonstrate that epigenetic silencing of
is associated with TSA development but is rarely observed in SSA/Ps. SMOC1 expression could thus be a diagnostic marker of serrated lesions, and
methylation could play a role in neoplastic pathways in TSAs and conventional adenomas.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>29435136</pmid><doi>10.18632/oncotarget.23523</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central; Free E- Journals |
| subjects | Research Paper |
| title | Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer |
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