MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells
Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer-associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)-21...
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| Veröffentlicht in: | Molecular medicine reports 2016-05, Vol.13 (5), p.4101-4107 |
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| creator | JIANG, SHUMEI WANG, RENBEN YAN, HONGJIANG JIN, LINZHI DOU, XUE CHEN, DONG |
| description | Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer-associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)-21 in the development of radiation resistance in non-small cell lung cancer cells. A radiation-resistant cell line was generated from A549 cells. Significant upregulation of miR-21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR-21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia-inducible factor-1α (HIF1α) was upregulated by miR-21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR-21-inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR-21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs. |
| doi_str_mv | 10.3892/mmr.2016.5010 |
| format | Article |
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Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)-21 in the development of radiation resistance in non-small cell lung cancer cells. A radiation-resistant cell line was generated from A549 cells. Significant upregulation of miR-21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR-21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia-inducible factor-1α (HIF1α) was upregulated by miR-21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR-21-inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR-21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2016.5010</identifier><identifier>PMID: 27035555</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Cancer therapies ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - radiotherapy ; Cell cycle ; Cell Line, Tumor ; Cellular signal transduction ; Development and progression ; Drug development ; Drug dosages ; Drug resistance ; Enzymes ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Glycolysis ; Health aspects ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-inducible factor 1a ; hypoxia-inducible factor-1α ; Kinases ; Lung cancer ; Lung cancer, Non-small cell ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lung Neoplasms - radiotherapy ; Metabolism ; MicroRNA ; MicroRNAs - genetics ; MicroRNAs - metabolism ; micrRNA-21 ; miRNA ; Neoplasm Proteins - biosynthesis ; Neoplasm Proteins - genetics ; non small cell lung cancer ; Non-small cell lung carcinoma ; Ovarian cancer ; Patient outcomes ; Properties ; Radiation therapy ; Radiation Tolerance ; Radioresistance ; Radiotherapy ; RNA, Neoplasm - genetics ; RNA, Neoplasm - metabolism ; siRNA ; Transcription ; Tumors ; Up-Regulation</subject><ispartof>Molecular medicine reports, 2016-05, Vol.13 (5), p.4101-4107</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-bd527b60576747200d81f90f3657acf1ecdedcb4bf90867bb10c1e93efcf79a93</citedby><cites>FETCH-LOGICAL-c459t-bd527b60576747200d81f90f3657acf1ecdedcb4bf90867bb10c1e93efcf79a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,5571,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27035555$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JIANG, SHUMEI</creatorcontrib><creatorcontrib>WANG, RENBEN</creatorcontrib><creatorcontrib>YAN, HONGJIANG</creatorcontrib><creatorcontrib>JIN, LINZHI</creatorcontrib><creatorcontrib>DOU, XUE</creatorcontrib><creatorcontrib>CHEN, DONG</creatorcontrib><title>MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer-associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)-21 in the development of radiation resistance in non-small cell lung cancer cells. A radiation-resistant cell line was generated from A549 cells. Significant upregulation of miR-21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR-21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia-inducible factor-1α (HIF1α) was upregulated by miR-21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR-21-inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR-21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.</description><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - radiotherapy</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cellular signal transduction</subject><subject>Development and progression</subject><subject>Drug development</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Enzymes</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Glycolysis</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Hypoxia-inducible factor 1a</subject><subject>hypoxia-inducible factor-1α</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - radiotherapy</subject><subject>Metabolism</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>micrRNA-21</subject><subject>miRNA</subject><subject>Neoplasm Proteins - biosynthesis</subject><subject>Neoplasm Proteins - genetics</subject><subject>non small cell lung cancer</subject><subject>Non-small cell lung carcinoma</subject><subject>Ovarian cancer</subject><subject>Patient outcomes</subject><subject>Properties</subject><subject>Radiation therapy</subject><subject>Radiation Tolerance</subject><subject>Radioresistance</subject><subject>Radiotherapy</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Neoplasm - metabolism</subject><subject>siRNA</subject><subject>Transcription</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptksuKFDEYhQtxcMbRpVsJuNBN2lwqlcqyGRwV5gKi65DKpTpDVVImVWA_ic8xL-IzmbLbQcUEkvDn-08O5FTVC4w2tBXk7TimDUG42TCE0aPqDHOBIUWofnw8EyH4afU05zuEGkaYeFKdEo4oK-Os-n7tdYqfbraQYDBGswxqthkkZbyafQwg2ezzrIK2YN6luPQ7sEzJ9iu43kcHdvspfvMK-mAW7bvBAqf0HBPEP-7hlOIYZ2tAP-x1HPZFDfgAQgwwj2oYgLZlGZbQA72-kn4V8rPqxKkh2-fH_bz6cvnu88UHeHX7_uPF9grqmokZdoYR3jWI8YbXnCBkWuwEcrRhXGmHrTbW6K7uSrFteNdhpLEV1DrtuFCCnldvDrrF59fF5lmOPq8OVLBxyRLzlnGKa9IW9NU_6F1cUijuJBaU1Lyp-R9UrwYrfXBxTkqvonJbMyowE4IUavMfqkxjR69jsM6X-l8N8NBQfivnZJ2ckh9V2kuM5BoEWYIg1yDINQiFf3k0u3SjNQ_0758vwOsDkCcVjDcxPzBFCWIKEYM1Rpj-BFp_vZQ</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>JIANG, SHUMEI</creator><creator>WANG, RENBEN</creator><creator>YAN, HONGJIANG</creator><creator>JIN, LINZHI</creator><creator>DOU, XUE</creator><creator>CHEN, DONG</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20160501</creationdate><title>MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells</title><author>JIANG, SHUMEI ; WANG, RENBEN ; YAN, HONGJIANG ; JIN, LINZHI ; DOU, XUE ; CHEN, DONG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-bd527b60576747200d81f90f3657acf1ecdedcb4bf90867bb10c1e93efcf79a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - radiotherapy</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cellular signal transduction</topic><topic>Development and progression</topic><topic>Drug development</topic><topic>Drug dosages</topic><topic>Drug resistance</topic><topic>Enzymes</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Glycolysis</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Hypoxia-inducible factor 1a</topic><topic>hypoxia-inducible factor-1α</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Lung cancer, Non-small cell</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - 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Academic</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JIANG, SHUMEI</au><au>WANG, RENBEN</au><au>YAN, HONGJIANG</au><au>JIN, LINZHI</au><au>DOU, XUE</au><au>CHEN, DONG</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>13</volume><issue>5</issue><spage>4101</spage><epage>4107</epage><pages>4101-4107</pages><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer-associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)-21 in the development of radiation resistance in non-small cell lung cancer cells. A radiation-resistant cell line was generated from A549 cells. Significant upregulation of miR-21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR-21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia-inducible factor-1α (HIF1α) was upregulated by miR-21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR-21-inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR-21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>27035555</pmid><doi>10.3892/mmr.2016.5010</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | Spandidos Publications Journals; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Cancer therapies Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - radiotherapy Cell cycle Cell Line, Tumor Cellular signal transduction Development and progression Drug development Drug dosages Drug resistance Enzymes Gene Expression Regulation, Neoplastic Genetic aspects Glycolysis Health aspects Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-inducible factor 1a hypoxia-inducible factor-1α Kinases Lung cancer Lung cancer, Non-small cell Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Lung Neoplasms - radiotherapy Metabolism MicroRNA MicroRNAs - genetics MicroRNAs - metabolism micrRNA-21 miRNA Neoplasm Proteins - biosynthesis Neoplasm Proteins - genetics non small cell lung cancer Non-small cell lung carcinoma Ovarian cancer Patient outcomes Properties Radiation therapy Radiation Tolerance Radioresistance Radiotherapy RNA, Neoplasm - genetics RNA, Neoplasm - metabolism siRNA Transcription Tumors Up-Regulation |
| title | MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells |
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