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MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This st...
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| Published in: | Carcinogenesis (New York) 2010-06, Vol.31 (6), p.1037-1044 |
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| container_end_page | 1044 |
| container_issue | 6 |
| container_start_page | 1037 |
| container_title | Carcinogenesis (New York) |
| container_volume | 31 |
| creator | Pang, Ronald T.K. Leung, Carmen O.N. Ye, Tian-Min Liu, Weimin Chiu, Philip C.N. Lam, Kevin K.W. Lee, Kai-Fai Yeung, William S.B. |
| description | MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3′ untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme. |
| doi_str_mv | 10.1093/carcin/bgq066 |
| format | article |
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However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3′ untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgq066</identifier><identifier>PMID: 20351093</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>3' Untranslated Regions ; Biological and medical sciences ; Blotting, Western ; Calcium-Binding Proteins - genetics ; Carcinogenesis, carcinogens and anticarcinogens ; Cell Line, Tumor ; Choriocarcinoma - genetics ; Choriocarcinoma - pathology ; Down-Regulation ; Female ; Female genital diseases ; Gene Knockdown Techniques ; Gynecology. Andrology. Obstetrics ; Humans ; Intercellular Signaling Peptides and Proteins - genetics ; Jagged-1 Protein ; Medical sciences ; Membrane Proteins - genetics ; MicroRNAs - physiology ; Neoplasm Invasiveness ; Receptor, Notch1 - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Serrate-Jagged Proteins ; Tumors ; Uterine Cervical Neoplasms - genetics ; Uterine Cervical Neoplasms - pathology</subject><ispartof>Carcinogenesis (New York), 2010-06, Vol.31 (6), p.1037-1044</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-11fc993f7452da5990e0d5ffe1aff3f887cb94e22ee78036209295f6eb49ea2a3</citedby><cites>FETCH-LOGICAL-c530t-11fc993f7452da5990e0d5ffe1aff3f887cb94e22ee78036209295f6eb49ea2a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22835218$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20351093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pang, Ronald T.K.</creatorcontrib><creatorcontrib>Leung, Carmen O.N.</creatorcontrib><creatorcontrib>Ye, Tian-Min</creatorcontrib><creatorcontrib>Liu, Weimin</creatorcontrib><creatorcontrib>Chiu, Philip C.N.</creatorcontrib><creatorcontrib>Lam, Kevin K.W.</creatorcontrib><creatorcontrib>Lee, Kai-Fai</creatorcontrib><creatorcontrib>Yeung, William S.B.</creatorcontrib><title>MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3′ untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme.</description><subject>3' Untranslated Regions</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Cell Line, Tumor</subject><subject>Choriocarcinoma - genetics</subject><subject>Choriocarcinoma - pathology</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gene Knockdown Techniques</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Jagged-1 Protein</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>MicroRNAs - physiology</subject><subject>Neoplasm Invasiveness</subject><subject>Receptor, Notch1 - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Serrate-Jagged Proteins</subject><subject>Tumors</subject><subject>Uterine Cervical Neoplasms - genetics</subject><subject>Uterine Cervical Neoplasms - pathology</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp9kctv1DAQxi0EotvCkSvyBdFLqN-Oj6U8SlWKREFCXCyvM84asvHWTgoc-N_JkqV74zTSzG9e34fQE0peUGL4iXfZx_5k2d4Qpe6hBRWKVIzW5D5aECp4xTkXB-iwlG-EUMWleYgOGOFy271Av99Hn9PHq9OKC4fLuNlkKAUKjv2tKzH1eFjlNLYr3KQffYZ27NywTaeAr9LgVxS7vsEXrm2hoVMX9pBvo3cdni9La_eX8KuUY9rnPHRdeYQeBNcVeLyLR-jzm9efzs6ryw9v352dXlZecjJUlAZvDA9aSNY4aQwB0sgQgLoQeKhr7ZdGAGMAuiZcMWKYkUHBUhhwzPEj9Hyeu8npZoQy2HUs2wtcD2ksVgtFpSG8nsjj_5JUE0OVVlpMaDWjk4ClZAh2k-Pa5V-WErtV187f2tmbiX-6Gz0u19Dc0f_MmIBnO8CVScCQXe9j2XOs5nJydr84lgF-3tVd_m6V5lra8y9f7UtxcU3Jq2tL-R-cM6lK</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Pang, Ronald T.K.</creator><creator>Leung, Carmen O.N.</creator><creator>Ye, Tian-Min</creator><creator>Liu, Weimin</creator><creator>Chiu, Philip C.N.</creator><creator>Lam, Kevin K.W.</creator><creator>Lee, Kai-Fai</creator><creator>Yeung, William S.B.</creator><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><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>7TM</scope><scope>7TO</scope><scope>H94</scope></search><sort><creationdate>20100601</creationdate><title>MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells</title><author>Pang, Ronald T.K. ; Leung, Carmen O.N. ; Ye, Tian-Min ; Liu, Weimin ; Chiu, Philip C.N. ; Lam, Kevin K.W. ; Lee, Kai-Fai ; Yeung, William S.B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c530t-11fc993f7452da5990e0d5ffe1aff3f887cb94e22ee78036209295f6eb49ea2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>3' Untranslated Regions</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Calcium-Binding Proteins - genetics</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Cell Line, Tumor</topic><topic>Choriocarcinoma - genetics</topic><topic>Choriocarcinoma - pathology</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gene Knockdown Techniques</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Jagged-1 Protein</topic><topic>Medical sciences</topic><topic>Membrane Proteins - genetics</topic><topic>MicroRNAs - physiology</topic><topic>Neoplasm Invasiveness</topic><topic>Receptor, Notch1 - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Serrate-Jagged Proteins</topic><topic>Tumors</topic><topic>Uterine Cervical Neoplasms - genetics</topic><topic>Uterine Cervical Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pang, Ronald T.K.</creatorcontrib><creatorcontrib>Leung, Carmen O.N.</creatorcontrib><creatorcontrib>Ye, Tian-Min</creatorcontrib><creatorcontrib>Liu, Weimin</creatorcontrib><creatorcontrib>Chiu, Philip C.N.</creatorcontrib><creatorcontrib>Lam, Kevin K.W.</creatorcontrib><creatorcontrib>Lee, Kai-Fai</creatorcontrib><creatorcontrib>Yeung, William S.B.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pang, Ronald T.K.</au><au>Leung, Carmen O.N.</au><au>Ye, Tian-Min</au><au>Liu, Weimin</au><au>Chiu, Philip C.N.</au><au>Lam, Kevin K.W.</au><au>Lee, Kai-Fai</au><au>Yeung, William S.B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>31</volume><issue>6</issue><spage>1037</spage><epage>1044</epage><pages>1037-1044</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><notes>ark:/67375/HXZ-B4JS10DS-1</notes><notes>istex:7D07D63D6072A1374965833E2F331B1E8022AF50</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3′ untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>20351093</pmid><doi>10.1093/carcin/bgq066</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current) |
| subjects | 3' Untranslated Regions Biological and medical sciences Blotting, Western Calcium-Binding Proteins - genetics Carcinogenesis, carcinogens and anticarcinogens Cell Line, Tumor Choriocarcinoma - genetics Choriocarcinoma - pathology Down-Regulation Female Female genital diseases Gene Knockdown Techniques Gynecology. Andrology. Obstetrics Humans Intercellular Signaling Peptides and Proteins - genetics Jagged-1 Protein Medical sciences Membrane Proteins - genetics MicroRNAs - physiology Neoplasm Invasiveness Receptor, Notch1 - genetics Reverse Transcriptase Polymerase Chain Reaction Serrate-Jagged Proteins Tumors Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - pathology |
| title | MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells |
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