miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells
In the present study, we demonstrated that the levels of DKK1 were decreased in serums and tissues of GC. DKK1 levels inversely correlated with tumor class, TNM stage, distant metastasis and lymph node metastasis of GC. GC patients with low DKK1 levels had a poor overall survival. DKK1 inhibited the...
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| Veröffentlicht in: | Oncotarget 2016-02, Vol.7 (6), p.7044-7054 |
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| creator | Jia, Xiaoting Li, Nan Peng, Cong Deng, Yingen Wang, Jia Deng, Min Lu, Minying Yin, Jiang Zheng, Guopei Liu, Haiying He, Zhimin |
| description | In the present study, we demonstrated that the levels of DKK1 were decreased in serums and tissues of GC. DKK1 levels inversely correlated with tumor class, TNM stage, distant metastasis and lymph node metastasis of GC. GC patients with low DKK1 levels had a poor overall survival. DKK1 inhibited the proliferation of GC cells in vitro and in vivo. DKK1 also inhibited invasion, but enhanced chemo-sensitivity of GC cells. Mechanically, miR-493 levels increased in GC and directly targeted and down-regulated DKK1 expression. In agreement, miR-493 promoted proliferation of GC cells in vitro and in vivo. MiR-493 also promoted invasion and chemo-resistance of GC cells. However, DKK1 overexpression reversed the effects of miR-493 on proliferation, invasion and chemo-sensitivity. Thus, our results provide new insight for the role of miR-493/DKK1 axis in GC. |
| doi_str_mv | 10.18632/oncotarget.6951 |
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DKK1 levels inversely correlated with tumor class, TNM stage, distant metastasis and lymph node metastasis of GC. GC patients with low DKK1 levels had a poor overall survival. DKK1 inhibited the proliferation of GC cells in vitro and in vivo. DKK1 also inhibited invasion, but enhanced chemo-sensitivity of GC cells. Mechanically, miR-493 levels increased in GC and directly targeted and down-regulated DKK1 expression. In agreement, miR-493 promoted proliferation of GC cells in vitro and in vivo. MiR-493 also promoted invasion and chemo-resistance of GC cells. However, DKK1 overexpression reversed the effects of miR-493 on proliferation, invasion and chemo-sensitivity. Thus, our results provide new insight for the role of miR-493/DKK1 axis in GC.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.6951</identifier><identifier>PMID: 26799283</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Apoptosis ; Blotting, Western ; Case-Control Studies ; Cell Movement ; Cell Proliferation ; Cohort Studies ; Down-Regulation ; Drug Resistance, Neoplasm - genetics ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - metabolism ; Lymphatic Metastasis ; Mice ; MicroRNAs - genetics ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Real-Time Polymerase Chain Reaction ; Research Paper ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Survival Rate ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2016-02, Vol.7 (6), p.7044-7054</ispartof><rights>Copyright: © 2016 Jia et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-a86d48be907034996bb1e7c083cbae7b3ba1f21a8cad450bd3b1d3938ccf2eac3</citedby><cites>FETCH-LOGICAL-c424t-a86d48be907034996bb1e7c083cbae7b3ba1f21a8cad450bd3b1d3938ccf2eac3</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/PMC4872767/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872767/$$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/26799283$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jia, Xiaoting</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Peng, Cong</creatorcontrib><creatorcontrib>Deng, Yingen</creatorcontrib><creatorcontrib>Wang, Jia</creatorcontrib><creatorcontrib>Deng, Min</creatorcontrib><creatorcontrib>Lu, Minying</creatorcontrib><creatorcontrib>Yin, Jiang</creatorcontrib><creatorcontrib>Zheng, Guopei</creatorcontrib><creatorcontrib>Liu, Haiying</creatorcontrib><creatorcontrib>He, Zhimin</creatorcontrib><title>miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>In the present study, we demonstrated that the levels of DKK1 were decreased in serums and tissues of GC. DKK1 levels inversely correlated with tumor class, TNM stage, distant metastasis and lymph node metastasis of GC. GC patients with low DKK1 levels had a poor overall survival. DKK1 inhibited the proliferation of GC cells in vitro and in vivo. DKK1 also inhibited invasion, but enhanced chemo-sensitivity of GC cells. Mechanically, miR-493 levels increased in GC and directly targeted and down-regulated DKK1 expression. In agreement, miR-493 promoted proliferation of GC cells in vitro and in vivo. MiR-493 also promoted invasion and chemo-resistance of GC cells. However, DKK1 overexpression reversed the effects of miR-493 on proliferation, invasion and chemo-sensitivity. Thus, our results provide new insight for the role of miR-493/DKK1 axis in GC.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Blotting, Western</subject><subject>Case-Control Studies</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cohort Studies</subject><subject>Down-Regulation</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Lymphatic Metastasis</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Staging</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Research Paper</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Survival Rate</subject><subject>Tumor Cells, Cultured</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1vFTEMjBCIVqV3TihHDmzJ126SCxIqn2olJATnyMl6X4N2k0eSV8S_Z7ctpfhiy-MZ2xpCnnN2xs0gxeucQm5QdtjOBtvzR-SYW2U70ffy8YP6iJzW-oOt0StthH1KjsSgrRVGHpOyxK-dspIuOEZoONJ3FxecjvlX6gruDjO0mBMNOU1YKt2XPMe1uum-ojFdQ91wSCMNV7jklVRjbZACrijdQW0lBhq2RqEB57k-I08mmCue3uUT8v3D-2_nn7rLLx8_n7-97IISqnVghlEZj5ZpJpW1g_ccdWBGBg-ovfTAJ8HBBBhVz_woPR-llSaESSAEeULe3OruD379LmBqBWa3L3GB8ttliO5_JMUrt8vXThkt9KBXgZd3AiX_PGBtbol1ewES5kN1XOtB6oGpbZTdjoaSay043a_hzN245f655Ta3VsqLh-fdE_56I_8AeO2Wnw</recordid><startdate>20160209</startdate><enddate>20160209</enddate><creator>Jia, Xiaoting</creator><creator>Li, Nan</creator><creator>Peng, Cong</creator><creator>Deng, Yingen</creator><creator>Wang, Jia</creator><creator>Deng, Min</creator><creator>Lu, Minying</creator><creator>Yin, Jiang</creator><creator>Zheng, Guopei</creator><creator>Liu, Haiying</creator><creator>He, Zhimin</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>20160209</creationdate><title>miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells</title><author>Jia, Xiaoting ; Li, Nan ; Peng, Cong ; Deng, Yingen ; Wang, Jia ; Deng, Min ; Lu, Minying ; Yin, Jiang ; Zheng, Guopei ; Liu, Haiying ; He, Zhimin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-a86d48be907034996bb1e7c083cbae7b3ba1f21a8cad450bd3b1d3938ccf2eac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Blotting, Western</topic><topic>Case-Control Studies</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cohort Studies</topic><topic>Down-Regulation</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Lymphatic Metastasis</topic><topic>Mice</topic><topic>MicroRNAs - genetics</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Staging</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Research Paper</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Survival Rate</topic><topic>Tumor Cells, Cultured</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Jia, Xiaoting</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Peng, Cong</creatorcontrib><creatorcontrib>Deng, Yingen</creatorcontrib><creatorcontrib>Wang, Jia</creatorcontrib><creatorcontrib>Deng, Min</creatorcontrib><creatorcontrib>Lu, Minying</creatorcontrib><creatorcontrib>Yin, Jiang</creatorcontrib><creatorcontrib>Zheng, Guopei</creatorcontrib><creatorcontrib>Liu, Haiying</creatorcontrib><creatorcontrib>He, Zhimin</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>Jia, Xiaoting</au><au>Li, Nan</au><au>Peng, Cong</au><au>Deng, Yingen</au><au>Wang, Jia</au><au>Deng, Min</au><au>Lu, Minying</au><au>Yin, Jiang</au><au>Zheng, Guopei</au><au>Liu, Haiying</au><au>He, Zhimin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-02-09</date><risdate>2016</risdate><volume>7</volume><issue>6</issue><spage>7044</spage><epage>7054</epage><pages>7044-7054</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>In the present study, we demonstrated that the levels of DKK1 were decreased in serums and tissues of GC. DKK1 levels inversely correlated with tumor class, TNM stage, distant metastasis and lymph node metastasis of GC. GC patients with low DKK1 levels had a poor overall survival. DKK1 inhibited the proliferation of GC cells in vitro and in vivo. DKK1 also inhibited invasion, but enhanced chemo-sensitivity of GC cells. Mechanically, miR-493 levels increased in GC and directly targeted and down-regulated DKK1 expression. In agreement, miR-493 promoted proliferation of GC cells in vitro and in vivo. MiR-493 also promoted invasion and chemo-resistance of GC cells. However, DKK1 overexpression reversed the effects of miR-493 on proliferation, invasion and chemo-sensitivity. Thus, our results provide new insight for the role of miR-493/DKK1 axis in GC.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>26799283</pmid><doi>10.18632/oncotarget.6951</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic Agents - pharmacology Apoptosis Blotting, Western Case-Control Studies Cell Movement Cell Proliferation Cohort Studies Down-Regulation Drug Resistance, Neoplasm - genetics Follow-Up Studies Gene Expression Regulation, Neoplastic Humans Immunoenzyme Techniques Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Lymphatic Metastasis Mice MicroRNAs - genetics Neoplasm Grading Neoplasm Invasiveness Neoplasm Staging Prognosis Real-Time Polymerase Chain Reaction Research Paper Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Stomach Neoplasms - drug therapy Stomach Neoplasms - genetics Stomach Neoplasms - pathology Survival Rate Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| title | miR-493 mediated DKK1 down-regulation confers proliferation, invasion and chemo-resistance in gastric cancer cells |
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