MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer
Past studies have shown that amplified insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1-R) signalling has an important role in colorectal cancer (CRC) development, progression and resistance to treatment. In this report, we demonstrate that downregulation of microRNA-497 (miR-497) as a result...
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| Veröffentlicht in: | Oncogene 2013-04, Vol.32 (15), p.1910-1920 |
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| creator | Guo, S T Jiang, C C Wang, G P Li, Y P Wang, C Y Guo, X Y Yang, R H Feng, Y Wang, F H Tseng, H-Y Thorne, R F Jin, L Zhang, X D |
| description | Past studies have shown that amplified insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1-R) signalling has an important role in colorectal cancer (CRC) development, progression and resistance to treatment. In this report, we demonstrate that downregulation of microRNA-497 (miR-497) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells. MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3′ untranslated region (3′UTR) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa. However, only overexpression of miR-497 led to suppression of the IGF1-R 3′UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells. This was associated with inhibition of cell survival, proliferation and invasion, and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil, and the death ligand tumour necrosis factor-related apoptosis-inducing ligand. The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling, as overexpression of an active form of Akt reversed its impact on cell survival and proliferation, recapitulating the effect of overexpression of IGF1-R. Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1, where these miRs are located at proximity. Similarly to miR-195, the members of the same miR family, miR-424 that was upregulated, and miR-15a, miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa, did not appear to have a role in regulating the expression of IGF1-R. Taken together, these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC. |
| doi_str_mv | 10.1038/onc.2012.214 |
| format | Article |
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In this report, we demonstrate that downregulation of microRNA-497 (miR-497) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells. MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3′ untranslated region (3′UTR) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa. However, only overexpression of miR-497 led to suppression of the IGF1-R 3′UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells. This was associated with inhibition of cell survival, proliferation and invasion, and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil, and the death ligand tumour necrosis factor-related apoptosis-inducing ligand. The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling, as overexpression of an active form of Akt reversed its impact on cell survival and proliferation, recapitulating the effect of overexpression of IGF1-R. Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1, where these miRs are located at proximity. Similarly to miR-195, the members of the same miR family, miR-424 that was upregulated, and miR-15a, miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa, did not appear to have a role in regulating the expression of IGF1-R. Taken together, these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2012.214</identifier><identifier>PMID: 22710713</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>3' Untranslated Regions ; 631/337/384/331 ; 631/67/1504/1885 ; 631/80/86 ; Apoptosis ; Apoptosis - genetics ; Care and treatment ; Cell Biology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival - genetics ; Cellular signal transduction ; Cisplatin - pharmacology ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Development and progression ; Disease Progression ; DNA Copy Number Variations ; Down-Regulation ; Drug Resistance, Neoplasm - genetics ; Fluorouracil - pharmacology ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Health aspects ; Human Genetics ; Humans ; Insulin-like growth factor 1 ; Insulin-Like Growth Factor I - metabolism ; Insulin-like growth factors ; Internal Medicine ; Medicine ; Medicine & Public Health ; MicroRNA ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Neoplasm Invasiveness - genetics ; Neurons ; Oncology ; Original ; original-article ; Phosphatidylinositol 3-Kinase - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Receptor, IGF Type 1 - metabolism ; Ribonucleic acid ; Risk factors ; RNA ; Signal Transduction - genetics ; Tumors</subject><ispartof>Oncogene, 2013-04, Vol.32 (15), p.1910-1920</ispartof><rights>The Author(s) 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 11, 2013</rights><rights>Copyright © 2013 Macmillan Publishers Limited 2013 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-b369065e4c30a8e6f95ba8f37679e39049e2229a8efd8ed59022643d2565c5813</citedby><cites>FETCH-LOGICAL-c550t-b369065e4c30a8e6f95ba8f37679e39049e2229a8efd8ed59022643d2565c5813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2012.214$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2012.214$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22710713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, S T</creatorcontrib><creatorcontrib>Jiang, C C</creatorcontrib><creatorcontrib>Wang, G P</creatorcontrib><creatorcontrib>Li, Y P</creatorcontrib><creatorcontrib>Wang, C Y</creatorcontrib><creatorcontrib>Guo, X Y</creatorcontrib><creatorcontrib>Yang, R H</creatorcontrib><creatorcontrib>Feng, Y</creatorcontrib><creatorcontrib>Wang, F H</creatorcontrib><creatorcontrib>Tseng, H-Y</creatorcontrib><creatorcontrib>Thorne, R F</creatorcontrib><creatorcontrib>Jin, L</creatorcontrib><creatorcontrib>Zhang, X D</creatorcontrib><title>MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Past studies have shown that amplified insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1-R) signalling has an important role in colorectal cancer (CRC) development, progression and resistance to treatment. In this report, we demonstrate that downregulation of microRNA-497 (miR-497) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells. MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3′ untranslated region (3′UTR) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa. However, only overexpression of miR-497 led to suppression of the IGF1-R 3′UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells. This was associated with inhibition of cell survival, proliferation and invasion, and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil, and the death ligand tumour necrosis factor-related apoptosis-inducing ligand. The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling, as overexpression of an active form of Akt reversed its impact on cell survival and proliferation, recapitulating the effect of overexpression of IGF1-R. Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1, where these miRs are located at proximity. Similarly to miR-195, the members of the same miR family, miR-424 that was upregulated, and miR-15a, miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa, did not appear to have a role in regulating the expression of IGF1-R. Taken together, these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.</description><subject>3' Untranslated Regions</subject><subject>631/337/384/331</subject><subject>631/67/1504/1885</subject><subject>631/80/86</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival - genetics</subject><subject>Cellular signal transduction</subject><subject>Cisplatin - pharmacology</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>DNA Copy Number Variations</subject><subject>Down-Regulation</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Fluorouracil - pharmacology</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Insulin-like growth factor 1</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Insulin-like growth factors</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>Neurons</subject><subject>Oncology</subject><subject>Original</subject><subject>original-article</subject><subject>Phosphatidylinositol 3-Kinase - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptor, IGF Type 1 - metabolism</subject><subject>Ribonucleic acid</subject><subject>Risk 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targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer</title><author>Guo, S T ; Jiang, C C ; Wang, G P ; Li, Y P ; Wang, C Y ; Guo, X Y ; Yang, R H ; Feng, Y ; Wang, F H ; Tseng, H-Y ; Thorne, R F ; Jin, L ; Zhang, X D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-b369065e4c30a8e6f95ba8f37679e39049e2229a8efd8ed59022643d2565c5813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3' Untranslated Regions</topic><topic>631/337/384/331</topic><topic>631/67/1504/1885</topic><topic>631/80/86</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Survival - genetics</topic><topic>Cellular signal transduction</topic><topic>Cisplatin - pharmacology</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>DNA Copy Number Variations</topic><topic>Down-Regulation</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Fluorouracil - pharmacology</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Insulin-like growth factor 1</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Insulin-like growth factors</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>Neurons</topic><topic>Oncology</topic><topic>Original</topic><topic>original-article</topic><topic>Phosphatidylinositol 3-Kinase - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptor, IGF Type 1 - metabolism</topic><topic>Ribonucleic acid</topic><topic>Risk factors</topic><topic>RNA</topic><topic>Signal Transduction - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, S T</creatorcontrib><creatorcontrib>Jiang, C C</creatorcontrib><creatorcontrib>Wang, G P</creatorcontrib><creatorcontrib>Li, Y P</creatorcontrib><creatorcontrib>Wang, C Y</creatorcontrib><creatorcontrib>Guo, X Y</creatorcontrib><creatorcontrib>Yang, R H</creatorcontrib><creatorcontrib>Feng, Y</creatorcontrib><creatorcontrib>Wang, F H</creatorcontrib><creatorcontrib>Tseng, H-Y</creatorcontrib><creatorcontrib>Thorne, R F</creatorcontrib><creatorcontrib>Jin, 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signalling has an important role in colorectal cancer (CRC) development, progression and resistance to treatment. In this report, we demonstrate that downregulation of microRNA-497 (miR-497) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells. MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3′ untranslated region (3′UTR) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa. However, only overexpression of miR-497 led to suppression of the IGF1-R 3′UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells. This was associated with inhibition of cell survival, proliferation and invasion, and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil, and the death ligand tumour necrosis factor-related apoptosis-inducing ligand. The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling, as overexpression of an active form of Akt reversed its impact on cell survival and proliferation, recapitulating the effect of overexpression of IGF1-R. Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1, where these miRs are located at proximity. Similarly to miR-195, the members of the same miR family, miR-424 that was upregulated, and miR-15a, miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa, did not appear to have a role in regulating the expression of IGF1-R. Taken together, these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22710713</pmid><doi>10.1038/onc.2012.214</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncogene, 2013-04, Vol.32 (15), p.1910-1920 |
| issn | 0950-9232 1476-5594 |
| language | eng |
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| source | MEDLINE; Nature Journals Online; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | 3' Untranslated Regions 631/337/384/331 631/67/1504/1885 631/80/86 Apoptosis Apoptosis - genetics Care and treatment Cell Biology Cell Line, Tumor Cell Proliferation Cell Survival - genetics Cellular signal transduction Cisplatin - pharmacology Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Development and progression Disease Progression DNA Copy Number Variations Down-Regulation Drug Resistance, Neoplasm - genetics Fluorouracil - pharmacology Gene Expression Regulation, Neoplastic Genetic aspects Health aspects Human Genetics Humans Insulin-like growth factor 1 Insulin-Like Growth Factor I - metabolism Insulin-like growth factors Internal Medicine Medicine Medicine & Public Health MicroRNA MicroRNAs - genetics MicroRNAs - metabolism Neoplasm Invasiveness - genetics Neurons Oncology Original original-article Phosphatidylinositol 3-Kinase - metabolism Proto-Oncogene Proteins c-akt - metabolism Receptor, IGF Type 1 - metabolism Ribonucleic acid Risk factors RNA Signal Transduction - genetics Tumors |
| title | MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T17%3A37%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MicroRNA-497%20targets%20insulin-like%20growth%20factor%201%20receptor%20and%20has%20a%20tumour%20suppressive%20role%20in%20human%20colorectal%20cancer&rft.jtitle=Oncogene&rft.au=Guo,%20S%20T&rft.date=2013-04-11&rft.volume=32&rft.issue=15&rft.spage=1910&rft.epage=1920&rft.pages=1910-1920&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/onc.2012.214&rft_dat=%3Cgale_pubme%3EA328163800%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1325573394&rft_id=info:pmid/22710713&rft_galeid=A328163800&rfr_iscdi=true |