miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma
•miR-1275 is markedly underexpressed in HCC and cirrhotic liver tissue.•miR-1275 reduces IGF2BP1, 2, and 3 mRNA, and directly binds to their 3′UTRs.•miR-1275 is a tumor suppressor, reducing several tumorigenic properties of HuH-7.•miR-1275 mimics and IGF2BP siRNAs significantly reduce IGF1R protein...
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| Veröffentlicht in: | FEBS letters 2015-08, Vol.589 (17), p.2257-2265 |
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| creator | Fawzy, Injie Omar Hamza, Mohammed Tarif Hosny, Karim Adel Esmat, Gamal El Tayebi, Hend Mohamed Abdelaziz, Ahmed Ihab |
| description | •miR-1275 is markedly underexpressed in HCC and cirrhotic liver tissue.•miR-1275 reduces IGF2BP1, 2, and 3 mRNA, and directly binds to their 3′UTRs.•miR-1275 is a tumor suppressor, reducing several tumorigenic properties of HuH-7.•miR-1275 mimics and IGF2BP siRNAs significantly reduce IGF1R protein and mRNA.•IGF1R is also directly targeted by miR-1275.
This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin-like growth factor-2-mRNA-binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR-1275 to simultaneously target the three IGF2BPs, and screening revealed miR-1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH-7 cells with miR-1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR-1275. Ectopic expression of miR-1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR-1275. These findings indicate that the tumor-suppressor miR-1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R. |
| doi_str_mv | 10.1016/j.febslet.2015.06.038 |
| format | Article |
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This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin-like growth factor-2-mRNA-binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR-1275 to simultaneously target the three IGF2BPs, and screening revealed miR-1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH-7 cells with miR-1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR-1275. Ectopic expression of miR-1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR-1275. These findings indicate that the tumor-suppressor miR-1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/j.febslet.2015.06.038</identifier><identifier>PMID: 26160756</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>3' Untranslated Regions - genetics ; Adult ; B2M ; Base Sequence ; beta-2 microglobulin ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; Cell Survival - genetics ; Female ; Gene Expression Regulation, Neoplastic ; HBV ; HCC ; HCV ; hepatitis B virus ; hepatitis C virus ; Hepatocellular carcinoma ; Humans ; IGF ; IGF1R ; IGF2BPs or IMPs ; IGFBPs ; insulin-like growth 1 receptor ; insulin-like growth binding proteins ; insulin-like growth factor ; Insulin-like growth factor 1 receptor (IGF1R) ; Insulin-like growth factor-2-mRNA-binding protein (IGF2BP or IMP) ; insulin-like growth-2-mRNA-binding proteins ; international normalized ratio for prothrombin time ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Male ; MELD ; microRNA ; MicroRNAs - genetics ; Middle Aged ; miR-1275 ; miRNA or miR ; Model for End-stage Liver Disease ; Posttranscriptional regulation ; PT-INR ; Receptor, IGF Type 1 ; Receptors, Somatomedin - genetics ; Receptors, Somatomedin - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Interference ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Sequence Homology, Nucleic Acid ; Tumor Burden - genetics ; Young Adult</subject><ispartof>FEBS letters, 2015-08, Vol.589 (17), p.2257-2265</ispartof><rights>2015 Federation of European Biochemical Societies</rights><rights>FEBS Letters 589 (2015) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><rights>Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5474-57d74ad3c8a711577493fb8bf9343622c249af53dc1a46b4b84eb0cb4c04aa413</citedby><cites>FETCH-LOGICAL-c5474-57d74ad3c8a711577493fb8bf9343622c249af53dc1a46b4b84eb0cb4c04aa413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.febslet.2015.06.038$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014579315005724$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,1427,3537,27901,27902,45550,45551,46384,46808,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26160756$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fawzy, Injie Omar</creatorcontrib><creatorcontrib>Hamza, Mohammed Tarif</creatorcontrib><creatorcontrib>Hosny, Karim Adel</creatorcontrib><creatorcontrib>Esmat, Gamal</creatorcontrib><creatorcontrib>El Tayebi, Hend Mohamed</creatorcontrib><creatorcontrib>Abdelaziz, Ahmed Ihab</creatorcontrib><title>miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>•miR-1275 is markedly underexpressed in HCC and cirrhotic liver tissue.•miR-1275 reduces IGF2BP1, 2, and 3 mRNA, and directly binds to their 3′UTRs.•miR-1275 is a tumor suppressor, reducing several tumorigenic properties of HuH-7.•miR-1275 mimics and IGF2BP siRNAs significantly reduce IGF1R protein and mRNA.•IGF1R is also directly targeted by miR-1275.
This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin-like growth factor-2-mRNA-binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR-1275 to simultaneously target the three IGF2BPs, and screening revealed miR-1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH-7 cells with miR-1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR-1275. Ectopic expression of miR-1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR-1275. These findings indicate that the tumor-suppressor miR-1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R.</description><subject>3' Untranslated Regions - genetics</subject><subject>Adult</subject><subject>B2M</subject><subject>Base Sequence</subject><subject>beta-2 microglobulin</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Cell Survival - genetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>HBV</subject><subject>HCC</subject><subject>HCV</subject><subject>hepatitis B virus</subject><subject>hepatitis C virus</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>IGF</subject><subject>IGF1R</subject><subject>IGF2BPs or IMPs</subject><subject>IGFBPs</subject><subject>insulin-like growth 1 receptor</subject><subject>insulin-like growth binding proteins</subject><subject>insulin-like growth factor</subject><subject>Insulin-like growth factor 1 receptor (IGF1R)</subject><subject>Insulin-like growth factor-2-mRNA-binding protein (IGF2BP or IMP)</subject><subject>insulin-like growth-2-mRNA-binding proteins</subject><subject>international normalized ratio for prothrombin time</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>MELD</subject><subject>microRNA</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miR-1275</subject><subject>miRNA or miR</subject><subject>Model for End-stage Liver Disease</subject><subject>Posttranscriptional regulation</subject><subject>PT-INR</subject><subject>Receptor, IGF Type 1</subject><subject>Receptors, Somatomedin - genetics</subject><subject>Receptors, Somatomedin - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA Interference</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Tumor Burden - genetics</subject><subject>Young Adult</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUtv1DAUhS0EokPhJ4C8ZJPUzzhhg6ZVp61UgVRgbdnOzYxHeQy2Q9UdPx1HM3QLC8u6V-ceH38XofeUlJTQ6mJfdmBjD6lkhMqSVCXh9Qu0orXiBRdV_RKtCKGikKrhZ-hNjHuS65o2r9EZq2hFlKxW6PfgHwrKlPyE1zj6cdsDHrwL08OXNU47k3AyYQsp5gLyCQD47mbDiiELCuvHNs_gQ5gS-DHiXW5AWFppHqaAt2F6TDvsR7yDg0mTg76fexOwM8H5cRrMW_SqM32Ed6f7HP3YXH-_ui3uv97cXa3vCyeFWn7RKmFa7mqjKJVKiYZ3trZdwwWvGHNMNKaTvHXUiMoKWwuwxFnhiDBGUH6OPh59c9afM8SkBx-XOGaEaY6aKkI55YTLLJVHacYQY4BOH4IfTHjSlOgFvt7rE3y9wNek0hl-nvtwemK2A7TPU39pZ8HtUfDoe3j6P1e9ub5k35ZNLoukkhCpmMhWn49WkJn98hB0dB5GB60P4JJuJ_-PtH8AV02toQ</recordid><startdate>20150804</startdate><enddate>20150804</enddate><creator>Fawzy, Injie Omar</creator><creator>Hamza, Mohammed Tarif</creator><creator>Hosny, Karim Adel</creator><creator>Esmat, Gamal</creator><creator>El Tayebi, Hend Mohamed</creator><creator>Abdelaziz, Ahmed Ihab</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20150804</creationdate><title>miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma</title><author>Fawzy, Injie Omar ; Hamza, Mohammed Tarif ; Hosny, Karim Adel ; Esmat, Gamal ; El Tayebi, Hend Mohamed ; Abdelaziz, Ahmed Ihab</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5474-57d74ad3c8a711577493fb8bf9343622c249af53dc1a46b4b84eb0cb4c04aa413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>3' Untranslated Regions - genetics</topic><topic>Adult</topic><topic>B2M</topic><topic>Base Sequence</topic><topic>beta-2 microglobulin</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Cell Survival - genetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>HBV</topic><topic>HCC</topic><topic>HCV</topic><topic>hepatitis B virus</topic><topic>hepatitis C virus</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>IGF</topic><topic>IGF1R</topic><topic>IGF2BPs or IMPs</topic><topic>IGFBPs</topic><topic>insulin-like growth 1 receptor</topic><topic>insulin-like growth binding proteins</topic><topic>insulin-like growth factor</topic><topic>Insulin-like growth factor 1 receptor (IGF1R)</topic><topic>Insulin-like growth factor-2-mRNA-binding protein (IGF2BP or IMP)</topic><topic>insulin-like growth-2-mRNA-binding proteins</topic><topic>international normalized ratio for prothrombin time</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>MELD</topic><topic>microRNA</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miR-1275</topic><topic>miRNA or miR</topic><topic>Model for End-stage Liver Disease</topic><topic>Posttranscriptional regulation</topic><topic>PT-INR</topic><topic>Receptor, IGF Type 1</topic><topic>Receptors, Somatomedin - genetics</topic><topic>Receptors, Somatomedin - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA Interference</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Tumor Burden - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fawzy, Injie Omar</creatorcontrib><creatorcontrib>Hamza, Mohammed Tarif</creatorcontrib><creatorcontrib>Hosny, Karim Adel</creatorcontrib><creatorcontrib>Esmat, Gamal</creatorcontrib><creatorcontrib>El Tayebi, Hend Mohamed</creatorcontrib><creatorcontrib>Abdelaziz, Ahmed Ihab</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fawzy, Injie Omar</au><au>Hamza, Mohammed Tarif</au><au>Hosny, Karim Adel</au><au>Esmat, Gamal</au><au>El Tayebi, Hend Mohamed</au><au>Abdelaziz, Ahmed Ihab</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2015-08-04</date><risdate>2015</risdate><volume>589</volume><issue>17</issue><spage>2257</spage><epage>2265</epage><pages>2257-2265</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>•miR-1275 is markedly underexpressed in HCC and cirrhotic liver tissue.•miR-1275 reduces IGF2BP1, 2, and 3 mRNA, and directly binds to their 3′UTRs.•miR-1275 is a tumor suppressor, reducing several tumorigenic properties of HuH-7.•miR-1275 mimics and IGF2BP siRNAs significantly reduce IGF1R protein and mRNA.•IGF1R is also directly targeted by miR-1275.
This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin-like growth factor-2-mRNA-binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR-1275 to simultaneously target the three IGF2BPs, and screening revealed miR-1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH-7 cells with miR-1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR-1275. Ectopic expression of miR-1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR-1275. These findings indicate that the tumor-suppressor miR-1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>26160756</pmid><doi>10.1016/j.febslet.2015.06.038</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3' Untranslated Regions - genetics Adult B2M Base Sequence beta-2 microglobulin Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Cell Survival - genetics Female Gene Expression Regulation, Neoplastic HBV HCC HCV hepatitis B virus hepatitis C virus Hepatocellular carcinoma Humans IGF IGF1R IGF2BPs or IMPs IGFBPs insulin-like growth 1 receptor insulin-like growth binding proteins insulin-like growth factor Insulin-like growth factor 1 receptor (IGF1R) Insulin-like growth factor-2-mRNA-binding protein (IGF2BP or IMP) insulin-like growth-2-mRNA-binding proteins international normalized ratio for prothrombin time Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Male MELD microRNA MicroRNAs - genetics Middle Aged miR-1275 miRNA or miR Model for End-stage Liver Disease Posttranscriptional regulation PT-INR Receptor, IGF Type 1 Receptors, Somatomedin - genetics Receptors, Somatomedin - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA Interference RNA, Messenger - genetics RNA, Messenger - metabolism RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Sequence Homology, Nucleic Acid Tumor Burden - genetics Young Adult |
| title | miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma |
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