MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4
Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo. By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopatholo...
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| Veröffentlicht in: | Oncotarget 2015-08, Vol.6 (25), p.21046-21063 |
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| creator | Xia, Xiang Zhang, Kundong Cen, Gang Jiang, Tao Cao, Jun Huang, Kejian Huang, Chen Zhao, Qian Qiu, Zhengjun |
| description | Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo.
By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed.
Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues.
MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4. |
| doi_str_mv | 10.18632/oncotarget.4124 |
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By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed.
Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues.
MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.4124</identifier><identifier>PMID: 26019136</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Aged ; Animals ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - metabolism ; Cell Movement ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lymphatic Metastasis ; Male ; Mice ; Mice, Nude ; MicroRNAs - metabolism ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreaticoduodenectomy ; Prognosis ; Real-Time Polymerase Chain Reaction ; Research Paper ; Smad4 Protein - metabolism ; Tissue Array Analysis</subject><ispartof>Oncotarget, 2015-08, Vol.6 (25), p.21046-21063</ispartof><rights>Copyright: © 2015 Xia et al. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-a53cca9e2a94e3980adaab7881cf144af5939008381feb631e1b382a848b9e003</citedby><cites>FETCH-LOGICAL-c354t-a53cca9e2a94e3980adaab7881cf144af5939008381feb631e1b382a848b9e003</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/PMC4673249/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673249/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26019136$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xia, Xiang</creatorcontrib><creatorcontrib>Zhang, Kundong</creatorcontrib><creatorcontrib>Cen, Gang</creatorcontrib><creatorcontrib>Jiang, Tao</creatorcontrib><creatorcontrib>Cao, Jun</creatorcontrib><creatorcontrib>Huang, Kejian</creatorcontrib><creatorcontrib>Huang, Chen</creatorcontrib><creatorcontrib>Zhao, Qian</creatorcontrib><creatorcontrib>Qiu, Zhengjun</creatorcontrib><title>MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo.
By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed.
Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues.
MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4.</description><subject>Aged</subject><subject>Animals</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - metabolism</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Transplantation</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreaticoduodenectomy</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Research Paper</subject><subject>Smad4 Protein - metabolism</subject><subject>Tissue Array Analysis</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUclOwzAQtRAIUOmdE8qRS4q3JPYFqSqrxCKxSNysiZmEoDQOdlqJv8dQljKXeZo382Y0j5B9RidM5YIfuc66AXyNw0QyLjfILtNSpzzLxOYa3iHjEF5pjEwWiuttssNzyjQT-S55um6sd3c301RQBqnok967uRswJD101iMMjU1shOg_qdpjCI3rkmUDSYd1pJeYeKwXbYSx7qrk_np6IvfIVgVtwPF3HpHHs9OH2UV6dXt-OZtepVZkckghE9aCRg5aotCKwjNAWSjFbMWkhCrTQlOqhGIVlrlgyEqhOCipSo2UihE5Xun2i3KOzxa7wUNret_Mwb8bB435z3TNi6nd0si8EFzqKHD4LeDd2wLDYOZNsNi20KFbBMMKxgtFKZOxla5a48tC8Fj9rmHUfHli_jwxn57EkYP1834HfhwQH0Ugiw0</recordid><startdate>20150828</startdate><enddate>20150828</enddate><creator>Xia, Xiang</creator><creator>Zhang, Kundong</creator><creator>Cen, Gang</creator><creator>Jiang, Tao</creator><creator>Cao, Jun</creator><creator>Huang, Kejian</creator><creator>Huang, Chen</creator><creator>Zhao, Qian</creator><creator>Qiu, Zhengjun</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150828</creationdate><title>MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4</title><author>Xia, Xiang ; Zhang, Kundong ; Cen, Gang ; Jiang, Tao ; Cao, Jun ; Huang, Kejian ; Huang, Chen ; Zhao, Qian ; Qiu, Zhengjun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-a53cca9e2a94e3980adaab7881cf144af5939008381feb631e1b382a848b9e003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - metabolism</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Transplantation</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreaticoduodenectomy</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Research Paper</topic><topic>Smad4 Protein - metabolism</topic><topic>Tissue Array Analysis</topic><toplevel>online_resources</toplevel><creatorcontrib>Xia, Xiang</creatorcontrib><creatorcontrib>Zhang, Kundong</creatorcontrib><creatorcontrib>Cen, Gang</creatorcontrib><creatorcontrib>Jiang, Tao</creatorcontrib><creatorcontrib>Cao, Jun</creatorcontrib><creatorcontrib>Huang, Kejian</creatorcontrib><creatorcontrib>Huang, Chen</creatorcontrib><creatorcontrib>Zhao, Qian</creatorcontrib><creatorcontrib>Qiu, Zhengjun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><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>Xia, Xiang</au><au>Zhang, Kundong</au><au>Cen, Gang</au><au>Jiang, Tao</au><au>Cao, Jun</au><au>Huang, Kejian</au><au>Huang, Chen</au><au>Zhao, Qian</au><au>Qiu, Zhengjun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2015-08-28</date><risdate>2015</risdate><volume>6</volume><issue>25</issue><spage>21046</spage><epage>21063</epage><pages>21046-21063</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo.
By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed.
Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues.
MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>26019136</pmid><doi>10.18632/oncotarget.4124</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Animals Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - metabolism Cell Movement Cell Proliferation Disease Progression Female Gene Expression Regulation, Neoplastic HEK293 Cells Humans Immunohistochemistry In Situ Hybridization Lymphatic Metastasis Male Mice Mice, Nude MicroRNAs - metabolism Middle Aged Multivariate Analysis Neoplasm Invasiveness Neoplasm Transplantation Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreaticoduodenectomy Prognosis Real-Time Polymerase Chain Reaction Research Paper Smad4 Protein - metabolism Tissue Array Analysis |
| title | MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4 |
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