Cellular stress induced alterations in microRNA let-7a and let-7b expression are dependent on p53
Genotoxic stressors, such as radiation, induce cellular damage that activates pre-programmed repair pathways, some of which involve microRNAs (miRNA) that alter gene expression. The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However,...
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| Veröffentlicht in: | PloS one 2011-10, Vol.6 (10), p.e24429-e24429 |
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| creator | Saleh, Anthony D Savage, Jason E Cao, Liu Soule, Benjamin P Ly, David DeGraff, William Harris, Curtis C Mitchell, James B Simone, Nicole L |
| description | Genotoxic stressors, such as radiation, induce cellular damage that activates pre-programmed repair pathways, some of which involve microRNAs (miRNA) that alter gene expression. The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However, the role and mechanism underlying regulation of let-7 genes in response to stress have yet to be elucidated. In this study we demonstrate that let-7a and let-7b expression decreases significantly following exposure to agents that induce stress including ionizing radiation. This decrease in expression is dependent on p53 and ATM in vitro and is not observed in a p53(-/-) colon cancer cell line (HCT116) or ATM(-/-) human fibroblasts. Chromatin Immunoprecipitation (ChIP) analysis showed p53 binding to a region upstream of the let-7 gene following radiation exposure. Luciferase transient transfections demonstrated that this p53 binding site is necessary for radiation-induced decreases in let-7 expression. A radiation-induced decrease in let-7a and let-7b expression is also observed in radiation-sensitive tissues in vivo and correlates with altered expression of proteins in p53-regulated pro-apoptotic signaling pathways. In contrast, this decreased expression is not observed in p53 knock-out mice suggesting that p53 directly repress let-7 expression. Exogenous expression of let-7a and let-7b increased radiation-induced cytotoxicity in HCT116 p53(+/+) cells but not HCT116 p53(-/-) cells. These results are the first demonstration of a mechanistic connection between the radiation-induced stress response and the regulation of miRNA and radiation-induced cytotoxicity and suggest that this process may be a molecular target for anticancer agents. |
| doi_str_mv | 10.1371/journal.pone.0024429 |
| format | Article |
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The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However, the role and mechanism underlying regulation of let-7 genes in response to stress have yet to be elucidated. In this study we demonstrate that let-7a and let-7b expression decreases significantly following exposure to agents that induce stress including ionizing radiation. This decrease in expression is dependent on p53 and ATM in vitro and is not observed in a p53(-/-) colon cancer cell line (HCT116) or ATM(-/-) human fibroblasts. Chromatin Immunoprecipitation (ChIP) analysis showed p53 binding to a region upstream of the let-7 gene following radiation exposure. Luciferase transient transfections demonstrated that this p53 binding site is necessary for radiation-induced decreases in let-7 expression. A radiation-induced decrease in let-7a and let-7b expression is also observed in radiation-sensitive tissues in vivo and correlates with altered expression of proteins in p53-regulated pro-apoptotic signaling pathways. In contrast, this decreased expression is not observed in p53 knock-out mice suggesting that p53 directly repress let-7 expression. Exogenous expression of let-7a and let-7b increased radiation-induced cytotoxicity in HCT116 p53(+/+) cells but not HCT116 p53(-/-) cells. These results are the first demonstration of a mechanistic connection between the radiation-induced stress response and the regulation of miRNA and radiation-induced cytotoxicity and suggest that this process may be a molecular target for anticancer agents.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0024429</identifier><identifier>PMID: 22022355</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animal tissues ; Animals ; Anticancer properties ; Antitumor agents ; Apoptosis ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Ataxia Telangiectasia Mutated Proteins ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Binding sites ; Biocompatibility ; Biology ; Cancer therapies ; Cell cycle ; Cell Cycle Proteins - metabolism ; Cell division ; Cell growth ; Cellular stress response ; Chromatin ; Colon ; Colon cancer ; Colorectal cancer ; Cytotoxicity ; Deoxyribonucleic acid ; Development and progression ; DNA ; DNA Damage ; DNA methylation ; DNA repair ; DNA-Binding Proteins - metabolism ; Enhancer Elements, Genetic - genetics ; Exposure ; Fibroblasts ; Gene expression ; Gene Expression Regulation, Neoplastic - radiation effects ; Gene regulation ; Genomics ; Genotoxicity ; HCT116 Cells ; Head & neck cancer ; Humans ; Immunoprecipitation ; Ionizing radiation ; Laboratories ; Luciferase ; Medicine ; Mice ; Mice, Inbred C57BL ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Oncology ; Ovarian cancer ; Oxidative Stress - genetics ; Oxidative Stress - radiation effects ; p53 Protein ; Penicillin ; Phosphorylation ; Phosphorylation - radiation effects ; Protein Binding - radiation effects ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; Radiation ; Radiation damage ; Radiation effects ; Radiation therapy ; Repair ; Ribonucleic acid ; RNA ; Signaling ; Stresses ; Thyroid gland ; Toxicity ; Transcription, Genetic - radiation effects ; Tumor proteins ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Ultraviolet Rays</subject><ispartof>PloS one, 2011-10, Vol.6 (10), p.e24429-e24429</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-2a69d73c91c3021a90cefd7d00015ae02353ac151a3ee9f8afc04d75b4a178ed3</citedby><cites>FETCH-LOGICAL-c691t-2a69d73c91c3021a90cefd7d00015ae02353ac151a3ee9f8afc04d75b4a178ed3</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/PMC3191136/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191136/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22022355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saleh, Anthony D</creatorcontrib><creatorcontrib>Savage, Jason E</creatorcontrib><creatorcontrib>Cao, Liu</creatorcontrib><creatorcontrib>Soule, Benjamin P</creatorcontrib><creatorcontrib>Ly, David</creatorcontrib><creatorcontrib>DeGraff, William</creatorcontrib><creatorcontrib>Harris, Curtis C</creatorcontrib><creatorcontrib>Mitchell, James B</creatorcontrib><creatorcontrib>Simone, Nicole L</creatorcontrib><title>Cellular stress induced alterations in microRNA let-7a and let-7b expression are dependent on p53</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Genotoxic stressors, such as radiation, induce cellular damage that activates pre-programmed repair pathways, some of which involve microRNAs (miRNA) that alter gene expression. The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However, the role and mechanism underlying regulation of let-7 genes in response to stress have yet to be elucidated. In this study we demonstrate that let-7a and let-7b expression decreases significantly following exposure to agents that induce stress including ionizing radiation. This decrease in expression is dependent on p53 and ATM in vitro and is not observed in a p53(-/-) colon cancer cell line (HCT116) or ATM(-/-) human fibroblasts. Chromatin Immunoprecipitation (ChIP) analysis showed p53 binding to a region upstream of the let-7 gene following radiation exposure. Luciferase transient transfections demonstrated that this p53 binding site is necessary for radiation-induced decreases in let-7 expression. A radiation-induced decrease in let-7a and let-7b expression is also observed in radiation-sensitive tissues in vivo and correlates with altered expression of proteins in p53-regulated pro-apoptotic signaling pathways. In contrast, this decreased expression is not observed in p53 knock-out mice suggesting that p53 directly repress let-7 expression. Exogenous expression of let-7a and let-7b increased radiation-induced cytotoxicity in HCT116 p53(+/+) cells but not HCT116 p53(-/-) cells. These results are the first demonstration of a mechanistic connection between the radiation-induced stress response and the regulation of miRNA and radiation-induced cytotoxicity and suggest that this process may be a molecular target for anticancer agents.</description><subject>Analysis</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Ataxia Telangiectasia Mutated Proteins</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Binding sites</subject><subject>Biocompatibility</subject><subject>Biology</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell division</subject><subject>Cell growth</subject><subject>Cellular stress response</subject><subject>Chromatin</subject><subject>Colon</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA methylation</subject><subject>DNA repair</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Enhancer Elements, Genetic - genetics</subject><subject>Exposure</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - radiation effects</subject><subject>Gene regulation</subject><subject>Genomics</subject><subject>Genotoxicity</subject><subject>HCT116 Cells</subject><subject>Head & neck cancer</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Ionizing radiation</subject><subject>Laboratories</subject><subject>Luciferase</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Oxidative Stress - genetics</subject><subject>Oxidative Stress - radiation effects</subject><subject>p53 Protein</subject><subject>Penicillin</subject><subject>Phosphorylation</subject><subject>Phosphorylation - radiation effects</subject><subject>Protein Binding - radiation effects</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Radiation</subject><subject>Radiation damage</subject><subject>Radiation effects</subject><subject>Radiation therapy</subject><subject>Repair</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signaling</subject><subject>Stresses</subject><subject>Thyroid gland</subject><subject>Toxicity</subject><subject>Transcription, Genetic - radiation effects</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Ultraviolet Rays</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1tr2zAUx83YWLtu32BshsHGHpLpYtnSyyCEXQJlhe7yKk6k48RFsVzJHt23n9K4JR59GHqQOPqdv47OJcteUjKnvKIfrvwQWnDzzrc4J4QVBVOPslOqOJuVjPDHR-eT7FmMV4QILsvyaXbCGGGMC3GawRKdGxyEPPYBY8yb1g4GbQ6uxwB949u9Ld81JvjLb4vcYT-rIIfWHo7rHG-6vWcicwiYW-ywtdj2eTJ0gj_PntTgIr4Y97Ps5-dPP5ZfZ-cXX1bLxfnMlIr2MwalshU3ihpOGAVFDNa2soQQKgBJCpeDoYICR1S1hNqQwlZiXQCtJFp-lr0-6HbORz1mJ2rKiSoEFZwlYnUgrIcr3YVmB-GP9tDoW4MPGw2hb4xDLZUUnNRoDS0LTFHVKKyUhtaMKMFE0vo4vjasdwlL_w3gJqLTm7bZ6o3_rTlVlPIyCbwbBYK_HjD2etdEk4oBLfohakVIyWUheCLf_EM-_LmR2kCKv2lrn541e029KKpSllKKKlHzB6i0LKYKp06qm2SfOLyfOCSmx5t-A0OMevX98v_Zi19T9u0Ru8XUbtvo3XDbcFOwOICp_2IMWN_nmBK9H4S7bOj9IOhxEJLbq-P63DvddT7_C0SFAjA</recordid><startdate>20111011</startdate><enddate>20111011</enddate><creator>Saleh, Anthony D</creator><creator>Savage, Jason E</creator><creator>Cao, Liu</creator><creator>Soule, Benjamin P</creator><creator>Ly, David</creator><creator>DeGraff, William</creator><creator>Harris, Curtis C</creator><creator>Mitchell, James B</creator><creator>Simone, Nicole L</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111011</creationdate><title>Cellular stress induced alterations in microRNA let-7a and let-7b expression are dependent on p53</title><author>Saleh, Anthony D ; Savage, Jason E ; Cao, Liu ; Soule, Benjamin P ; Ly, David ; DeGraff, William ; Harris, Curtis C ; Mitchell, James B ; Simone, Nicole L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-2a69d73c91c3021a90cefd7d00015ae02353ac151a3ee9f8afc04d75b4a178ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analysis</topic><topic>Animal tissues</topic><topic>Animals</topic><topic>Anticancer properties</topic><topic>Antitumor agents</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saleh, Anthony D</au><au>Savage, Jason E</au><au>Cao, Liu</au><au>Soule, Benjamin P</au><au>Ly, David</au><au>DeGraff, William</au><au>Harris, Curtis C</au><au>Mitchell, James B</au><au>Simone, Nicole L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cellular stress induced alterations in microRNA let-7a and let-7b expression are dependent on p53</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-10-11</date><risdate>2011</risdate><volume>6</volume><issue>10</issue><spage>e24429</spage><epage>e24429</epage><pages>e24429-e24429</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Genotoxic stressors, such as radiation, induce cellular damage that activates pre-programmed repair pathways, some of which involve microRNAs (miRNA) that alter gene expression. The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However, the role and mechanism underlying regulation of let-7 genes in response to stress have yet to be elucidated. In this study we demonstrate that let-7a and let-7b expression decreases significantly following exposure to agents that induce stress including ionizing radiation. This decrease in expression is dependent on p53 and ATM in vitro and is not observed in a p53(-/-) colon cancer cell line (HCT116) or ATM(-/-) human fibroblasts. Chromatin Immunoprecipitation (ChIP) analysis showed p53 binding to a region upstream of the let-7 gene following radiation exposure. Luciferase transient transfections demonstrated that this p53 binding site is necessary for radiation-induced decreases in let-7 expression. A radiation-induced decrease in let-7a and let-7b expression is also observed in radiation-sensitive tissues in vivo and correlates with altered expression of proteins in p53-regulated pro-apoptotic signaling pathways. In contrast, this decreased expression is not observed in p53 knock-out mice suggesting that p53 directly repress let-7 expression. Exogenous expression of let-7a and let-7b increased radiation-induced cytotoxicity in HCT116 p53(+/+) cells but not HCT116 p53(-/-) cells. These results are the first demonstration of a mechanistic connection between the radiation-induced stress response and the regulation of miRNA and radiation-induced cytotoxicity and suggest that this process may be a molecular target for anticancer agents.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22022355</pmid><doi>10.1371/journal.pone.0024429</doi><tpages>e24429</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-10, Vol.6 (10), p.e24429-e24429 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1309451532 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Animal tissues Animals Anticancer properties Antitumor agents Apoptosis Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Ataxia Telangiectasia Mutated Proteins bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Binding sites Biocompatibility Biology Cancer therapies Cell cycle Cell Cycle Proteins - metabolism Cell division Cell growth Cellular stress response Chromatin Colon Colon cancer Colorectal cancer Cytotoxicity Deoxyribonucleic acid Development and progression DNA DNA Damage DNA methylation DNA repair DNA-Binding Proteins - metabolism Enhancer Elements, Genetic - genetics Exposure Fibroblasts Gene expression Gene Expression Regulation, Neoplastic - radiation effects Gene regulation Genomics Genotoxicity HCT116 Cells Head & neck cancer Humans Immunoprecipitation Ionizing radiation Laboratories Luciferase Medicine Mice Mice, Inbred C57BL MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Oncology Ovarian cancer Oxidative Stress - genetics Oxidative Stress - radiation effects p53 Protein Penicillin Phosphorylation Phosphorylation - radiation effects Protein Binding - radiation effects Protein-Serine-Threonine Kinases - metabolism Proteins Radiation Radiation damage Radiation effects Radiation therapy Repair Ribonucleic acid RNA Signaling Stresses Thyroid gland Toxicity Transcription, Genetic - radiation effects Tumor proteins Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Ultraviolet Rays |
| title | Cellular stress induced alterations in microRNA let-7a and let-7b expression are dependent on p53 |
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