Dysregulation of MicroRNA-34a Expression in Colorectal Cancer Inhibits the Phosphorylation of FAK Via VEGF
Background MicroRNAs (miRs) are small non-coding RNAs that play important roles in cancer development where they can act as oncogenes or as tumor-suppressors. MiR-34a is a tumor suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a...
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| Veröffentlicht in: | Digestive diseases and sciences 2014-05, Vol.59 (5), p.958-967 |
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| creator | Zhang, Danhua Zhou, Jianping Dong, Ming |
| description | Background
MicroRNAs (miRs) are small non-coding RNAs that play important roles in cancer development where they can act as oncogenes or as tumor-suppressors. MiR-34a is a tumor suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in colorectal cancer (CRC).
Aim
This study aims to show the dysregulation of miR-34a in CRC and to characterize the function and mechanism of miR-34a in CRC cell lines.
Methods
The expression of miR-34a was detected using real-time PCR on CRC tissues and adjacent non-tumorous tissues. The ELISA was used to assess vascular endothelial growth factor (VEGF). The focal adhesion kinase (FAK) and phosphorylated FAK Y397 (pY397FAK) were measured by Western blot. The functions of miR-34a in vivo were measured by migration, invasion, CCK-8 assay and flow cytometry.
Results
MiR-34a was significantly downregulated and pY397FAK was upregulated in CRC cancer tissues. It plays an important role in inhibiting migration and invasion and in increasing apoptosis of CRC cells. Bioinformatic analysis suggested that VEGF may be a target of miR-34a, and this hypothesis was proved by ELISA and RT-PCR. The level of pY397FAK that could be activated by VEGF was downregulated in miR-34a overexpression CRC cell lines. The phosphorylation of FAK at 397 sites in miR-34a-stable cell lines was completely rescued by extra VEGF treatment.
Conclusion
MiR-34a is frequently downregulated in CRC and modulates the phosphorylation of FAK by negatively regulating VEGF. |
| doi_str_mv | 10.1007/s10620-013-2983-4 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1942217421</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A712942938</galeid><sourcerecordid>A712942938</sourcerecordid><originalsourceid>FETCH-LOGICAL-c538t-1b74ec02422db417111a12abbc0e8e96866d02ca47a8fc8a0c6c96148e72a0093</originalsourceid><addsrcrecordid>eNqFkk1vEzEQhi0EoqHwA7ggS1y4bPHYXtt7jEJSKsqHEPRqeR1v4mhjp_auRP49XqVQQCDkgz_mmdczmheh50AugBD5OgMRlFQEWEUbxSr-AM2gluVWC_UQzQiIcgYQZ-hJzjtCSCNBPEZnlDNJpOIztHtzzMltxt4MPgYcO_ze2xQ_f5hXjBu8_HZILucp5ANexD4mZwfT44UJ1iV8Fba-9UPGw9bhT9uYD9uYjvdiq_k7fOMNvllerp6iR53ps3t2t5-jr6vll8Xb6vrj5dVifl3ZmqmhglZyZwnllK5bDhIADFDTtpY45RqhhFgTag2XRnVWGWKFbQRw5SQ1pUN2jl6ddA8p3o4uD3rvs3V9b4KLY9bQFGmQnML_0RpUKYQxXtCXf6C7OKZQGpkoWXNK6vqe2pjeaR-6OCRjJ1E9l0DLzw1Thbr4C1XW2u29jcF1vrz_lgCnhDKaXObV6UPye5OOGoierKBPVtDFCnqygp4KfnFX8Nju3fpnxo_ZF4CegFxCYePSLx39U_U7j8a6CQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1517542055</pqid></control><display><type>article</type><title>Dysregulation of MicroRNA-34a Expression in Colorectal Cancer Inhibits the Phosphorylation of FAK Via VEGF</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Zhang, Danhua ; Zhou, Jianping ; Dong, Ming</creator><creatorcontrib>Zhang, Danhua ; Zhou, Jianping ; Dong, Ming</creatorcontrib><description>Background
MicroRNAs (miRs) are small non-coding RNAs that play important roles in cancer development where they can act as oncogenes or as tumor-suppressors. MiR-34a is a tumor suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in colorectal cancer (CRC).
Aim
This study aims to show the dysregulation of miR-34a in CRC and to characterize the function and mechanism of miR-34a in CRC cell lines.
Methods
The expression of miR-34a was detected using real-time PCR on CRC tissues and adjacent non-tumorous tissues. The ELISA was used to assess vascular endothelial growth factor (VEGF). The focal adhesion kinase (FAK) and phosphorylated FAK Y397 (pY397FAK) were measured by Western blot. The functions of miR-34a in vivo were measured by migration, invasion, CCK-8 assay and flow cytometry.
Results
MiR-34a was significantly downregulated and pY397FAK was upregulated in CRC cancer tissues. It plays an important role in inhibiting migration and invasion and in increasing apoptosis of CRC cells. Bioinformatic analysis suggested that VEGF may be a target of miR-34a, and this hypothesis was proved by ELISA and RT-PCR. The level of pY397FAK that could be activated by VEGF was downregulated in miR-34a overexpression CRC cell lines. The phosphorylation of FAK at 397 sites in miR-34a-stable cell lines was completely rescued by extra VEGF treatment.
Conclusion
MiR-34a is frequently downregulated in CRC and modulates the phosphorylation of FAK by negatively regulating VEGF.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-013-2983-4</identifier><identifier>PMID: 24370784</identifier><identifier>CODEN: DDSCDJ</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analysis ; Binding Sites ; Biochemistry ; Cell Line, Tumor ; Colorectal cancer ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Development and progression ; Enzyme-linked immunosorbent assay ; Female ; Focal Adhesion Kinase 1 - genetics ; Focal Adhesion Kinase 1 - metabolism ; Gastroenterology ; Gene Expression Regulation, Neoplastic - physiology ; Hepatology ; Humans ; Male ; Medicine ; Medicine & Public Health ; MicroRNA ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; Oncology ; Original Article ; Phosphorylation ; Transplant Surgery ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Digestive diseases and sciences, 2014-05, Vol.59 (5), p.958-967</ispartof><rights>Springer Science+Business Media New York 2013</rights><rights>COPYRIGHT 2014 Springer</rights><rights>Springer Science+Business Media New York 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-1b74ec02422db417111a12abbc0e8e96866d02ca47a8fc8a0c6c96148e72a0093</citedby><cites>FETCH-LOGICAL-c538t-1b74ec02422db417111a12abbc0e8e96866d02ca47a8fc8a0c6c96148e72a0093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10620-013-2983-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10620-013-2983-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24370784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Danhua</creatorcontrib><creatorcontrib>Zhou, Jianping</creatorcontrib><creatorcontrib>Dong, Ming</creatorcontrib><title>Dysregulation of MicroRNA-34a Expression in Colorectal Cancer Inhibits the Phosphorylation of FAK Via VEGF</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>Background
MicroRNAs (miRs) are small non-coding RNAs that play important roles in cancer development where they can act as oncogenes or as tumor-suppressors. MiR-34a is a tumor suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in colorectal cancer (CRC).
Aim
This study aims to show the dysregulation of miR-34a in CRC and to characterize the function and mechanism of miR-34a in CRC cell lines.
Methods
The expression of miR-34a was detected using real-time PCR on CRC tissues and adjacent non-tumorous tissues. The ELISA was used to assess vascular endothelial growth factor (VEGF). The focal adhesion kinase (FAK) and phosphorylated FAK Y397 (pY397FAK) were measured by Western blot. The functions of miR-34a in vivo were measured by migration, invasion, CCK-8 assay and flow cytometry.
Results
MiR-34a was significantly downregulated and pY397FAK was upregulated in CRC cancer tissues. It plays an important role in inhibiting migration and invasion and in increasing apoptosis of CRC cells. Bioinformatic analysis suggested that VEGF may be a target of miR-34a, and this hypothesis was proved by ELISA and RT-PCR. The level of pY397FAK that could be activated by VEGF was downregulated in miR-34a overexpression CRC cell lines. The phosphorylation of FAK at 397 sites in miR-34a-stable cell lines was completely rescued by extra VEGF treatment.
Conclusion
MiR-34a is frequently downregulated in CRC and modulates the phosphorylation of FAK by negatively regulating VEGF.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Binding Sites</subject><subject>Biochemistry</subject><subject>Cell Line, Tumor</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Development and progression</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Focal Adhesion Kinase 1 - genetics</subject><subject>Focal Adhesion Kinase 1 - metabolism</subject><subject>Gastroenterology</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Phosphorylation</subject><subject>Transplant Surgery</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkk1vEzEQhi0EoqHwA7ggS1y4bPHYXtt7jEJSKsqHEPRqeR1v4mhjp_auRP49XqVQQCDkgz_mmdczmheh50AugBD5OgMRlFQEWEUbxSr-AM2gluVWC_UQzQiIcgYQZ-hJzjtCSCNBPEZnlDNJpOIztHtzzMltxt4MPgYcO_ze2xQ_f5hXjBu8_HZILucp5ANexD4mZwfT44UJ1iV8Fba-9UPGw9bhT9uYD9uYjvdiq_k7fOMNvllerp6iR53ps3t2t5-jr6vll8Xb6vrj5dVifl3ZmqmhglZyZwnllK5bDhIADFDTtpY45RqhhFgTag2XRnVWGWKFbQRw5SQ1pUN2jl6ddA8p3o4uD3rvs3V9b4KLY9bQFGmQnML_0RpUKYQxXtCXf6C7OKZQGpkoWXNK6vqe2pjeaR-6OCRjJ1E9l0DLzw1Thbr4C1XW2u29jcF1vrz_lgCnhDKaXObV6UPye5OOGoierKBPVtDFCnqygp4KfnFX8Nju3fpnxo_ZF4CegFxCYePSLx39U_U7j8a6CQ</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Zhang, Danhua</creator><creator>Zhou, Jianping</creator><creator>Dong, Ming</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20140501</creationdate><title>Dysregulation of MicroRNA-34a Expression in Colorectal Cancer Inhibits the Phosphorylation of FAK Via VEGF</title><author>Zhang, Danhua ; Zhou, Jianping ; Dong, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-1b74ec02422db417111a12abbc0e8e96866d02ca47a8fc8a0c6c96148e72a0093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Binding Sites</topic><topic>Biochemistry</topic><topic>Cell Line, Tumor</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Development and progression</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Focal Adhesion Kinase 1 - genetics</topic><topic>Focal Adhesion Kinase 1 - metabolism</topic><topic>Gastroenterology</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Phosphorylation</topic><topic>Transplant Surgery</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Danhua</creatorcontrib><creatorcontrib>Zhou, Jianping</creatorcontrib><creatorcontrib>Dong, Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Danhua</au><au>Zhou, Jianping</au><au>Dong, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dysregulation of MicroRNA-34a Expression in Colorectal Cancer Inhibits the Phosphorylation of FAK Via VEGF</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>59</volume><issue>5</issue><spage>958</spage><epage>967</epage><pages>958-967</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><coden>DDSCDJ</coden><abstract>Background
MicroRNAs (miRs) are small non-coding RNAs that play important roles in cancer development where they can act as oncogenes or as tumor-suppressors. MiR-34a is a tumor suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in colorectal cancer (CRC).
Aim
This study aims to show the dysregulation of miR-34a in CRC and to characterize the function and mechanism of miR-34a in CRC cell lines.
Methods
The expression of miR-34a was detected using real-time PCR on CRC tissues and adjacent non-tumorous tissues. The ELISA was used to assess vascular endothelial growth factor (VEGF). The focal adhesion kinase (FAK) and phosphorylated FAK Y397 (pY397FAK) were measured by Western blot. The functions of miR-34a in vivo were measured by migration, invasion, CCK-8 assay and flow cytometry.
Results
MiR-34a was significantly downregulated and pY397FAK was upregulated in CRC cancer tissues. It plays an important role in inhibiting migration and invasion and in increasing apoptosis of CRC cells. Bioinformatic analysis suggested that VEGF may be a target of miR-34a, and this hypothesis was proved by ELISA and RT-PCR. The level of pY397FAK that could be activated by VEGF was downregulated in miR-34a overexpression CRC cell lines. The phosphorylation of FAK at 397 sites in miR-34a-stable cell lines was completely rescued by extra VEGF treatment.
Conclusion
MiR-34a is frequently downregulated in CRC and modulates the phosphorylation of FAK by negatively regulating VEGF.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>24370784</pmid><doi>10.1007/s10620-013-2983-4</doi><tpages>10</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Analysis Binding Sites Biochemistry Cell Line, Tumor Colorectal cancer Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Development and progression Enzyme-linked immunosorbent assay Female Focal Adhesion Kinase 1 - genetics Focal Adhesion Kinase 1 - metabolism Gastroenterology Gene Expression Regulation, Neoplastic - physiology Hepatology Humans Male Medicine Medicine & Public Health MicroRNA MicroRNAs - genetics MicroRNAs - metabolism Middle Aged Oncology Original Article Phosphorylation Transplant Surgery Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism |
| title | Dysregulation of MicroRNA-34a Expression in Colorectal Cancer Inhibits the Phosphorylation of FAK Via VEGF |
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