Aberrant miR-1246 expression promotes radioresistance in non-small cell lung cancer: a potential prognostic biomarker and radiotherapy sensitization target
Identifieur interne : 000F33 ( Ncbi/Merge ); précédent : 000F32; suivant : 000F34Aberrant miR-1246 expression promotes radioresistance in non-small cell lung cancer: a potential prognostic biomarker and radiotherapy sensitization target
Auteurs : Liyuan Fan [République populaire de Chine] ; Juan Wang [République populaire de Chine] ; Qiang Cao [République populaire de Chine] ; Xiuping Ding [République populaire de Chine] ; Baosheng Li [République populaire de Chine]Source :
- American Journal of Cancer Research [ 2156-6976 ] ; 2020.
Abstract
Radiosensitivity varies among patients with non-small cell lung cancer (NSCLC). In this work, we aimed to investigate microRNAs associated with this heterogeneity among individuals. We selected miR-1246 from the microRNAs that were revealed by microarray experiments to be differentially expressed between radioresistant and parental cell lines. Both intracellular and extracellular miR-1246 was found to be upregulated after irradiation in a time-dependent pattern, resulting in increased radioresistance of NSCLC cells. We found that mTOR was a direct target gene of miR-1246, which mediated miR-1246-induced autophagy activation. Yin Yang-1 (YY1) was demonstrated to be a new transcription factor that regulates miR-1246 and CDR1as was found to be a circular RNA that sequesters miR-1246, which was confirmed in NSCLC cells and clinical samples. Finally, combining these data with the results from The Cancer Genome Atlas (TCGA), we verified that miR-1246 could be used as a biomarker to predict NSCLC patients’ radiosensitivity and prognosis. Overall, our study fully investigated the effect of miR-1246 on radiosensitivity and comprehensively investigated the potential of miR-1246 as a prognostic biomarker and radiotherapy sensitization target.
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PubMed: 32064170
PubMed Central: 7017745
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id="au2"><institution>Cheeloo College of Medicine, Shandong University</institution><addr-line>Jinan 250112, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jinan 250112</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Juan" sort="Wang, Juan" uniqKey="Wang J" first="Juan" last="Wang">Juan Wang</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences</institution><addr-line>Jinan 250117, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jinan 250117</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Qiang" sort="Cao, Qiang" uniqKey="Cao Q" first="Qiang" last="Cao">Qiang Cao</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>School of Computer Science and 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Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences</institution><addr-line>Jinan 250117, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jinan 250117</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Cheeloo College of Medicine, Shandong University</institution><addr-line>Jinan 250112, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jinan 250112</wicri:regionArea></affiliation></author></analytic><series><title level="j">American Journal of Cancer Research</title><idno type="eISSN">2156-6976</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Radiosensitivity varies among patients with non-small cell lung cancer (NSCLC). In this work, we aimed to investigate microRNAs associated with this heterogeneity among individuals. We selected miR-1246 from the microRNAs that were revealed by microarray experiments to be differentially expressed between radioresistant and parental cell lines. Both intracellular and extracellular miR-1246 was found to be upregulated after irradiation in a time-dependent pattern, resulting in increased radioresistance of NSCLC cells. We found that mTOR was a direct target gene of miR-1246, which mediated miR-1246-induced autophagy activation. Yin Yang-1 (YY1) was demonstrated to be a new transcription factor that regulates miR-1246 and CDR1as was found to be a circular RNA that sequesters miR-1246, which was confirmed in NSCLC cells and clinical samples. Finally, combining these data with the results from The Cancer Genome Atlas (TCGA), we verified that miR-1246 could be used as a biomarker to predict NSCLC patients’ radiosensitivity and prognosis. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Cancer Res</journal-id><journal-id journal-id-type="iso-abbrev">Am J Cancer Res</journal-id><journal-id journal-id-type="publisher-id">ajcr</journal-id><journal-title-group><journal-title>American Journal of Cancer Research</journal-title></journal-title-group><issn pub-type="epub">2156-6976</issn><publisher><publisher-name>e-Century Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32064170</article-id><article-id pub-id-type="pmc">7017745</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Aberrant miR-1246 expression promotes radioresistance in non-small cell lung cancer: a potential prognostic biomarker and radiotherapy sensitization target</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Fan</surname><given-names>Liyuan</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Juan</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Qiang</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ding</surname><given-names>Xiuping</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Baosheng</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref></contrib><aff id="au1"><label>1</label><institution>Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences</institution><addr-line>Jinan 250117, China</addr-line></aff><aff id="au2"><label>2</label><institution>Cheeloo College of Medicine, Shandong University</institution><addr-line>Jinan 250112, China</addr-line></aff><aff id="au3"><label>3</label><institution>School of Computer Science and Engineering, Southeast University</institution><addr-line>Nanjing 211189, China</addr-line></aff></contrib-group><author-notes><corresp><bold>Address correspondence to:</bold> Baosheng Li, Department of Radiation, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117, Shandong, China; Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan 250112, Shandong, China. E-mail: <email>baoshli1963@163.com</email>; <email>bsli@sdfmu.eud.cn</email></corresp></author-notes><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>01</day><month>1</month><year>2020</year></pub-date><volume>10</volume><issue>1</issue><fpage>314</fpage><lpage>335</lpage><history><date date-type="received"><day>15</day><month>10</month><year>2019</year></date><date date-type="accepted"><day>22</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>AJCR Copyright © 2020</copyright-statement><copyright-year>2020</copyright-year></permissions><abstract><p>Radiosensitivity varies among patients with non-small cell lung cancer (NSCLC). In this work, we aimed to investigate microRNAs associated with this heterogeneity among individuals. We selected miR-1246 from the microRNAs that were revealed by microarray experiments to be differentially expressed between radioresistant and parental cell lines. Both intracellular and extracellular miR-1246 was found to be upregulated after irradiation in a time-dependent pattern, resulting in increased radioresistance of NSCLC cells. We found that mTOR was a direct target gene of miR-1246, which mediated miR-1246-induced autophagy activation. Yin Yang-1 (YY1) was demonstrated to be a new transcription factor that regulates miR-1246 and CDR1as was found to be a circular RNA that sequesters miR-1246, which was confirmed in NSCLC cells and clinical samples. Finally, combining these data with the results from The Cancer Genome Atlas (TCGA), we verified that miR-1246 could be used as a biomarker to predict NSCLC patients’ radiosensitivity and prognosis. Overall, our study fully investigated the effect of miR-1246 on radiosensitivity and comprehensively investigated the potential of miR-1246 as a prognostic biomarker and radiotherapy sensitization target.</p></abstract><kwd-group><kwd>miR-1246</kwd><kwd>mTOR</kwd><kwd>YY1</kwd><kwd>CDR1as</kwd><kwd>radiosensitivity</kwd><kwd>autophagy</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Fan, Liyuan" sort="Fan, Liyuan" uniqKey="Fan L" first="Liyuan" last="Fan">Liyuan Fan</name></noRegion><name sortKey="Cao, Qiang" sort="Cao, Qiang" uniqKey="Cao Q" first="Qiang" last="Cao">Qiang Cao</name><name sortKey="Ding, Xiuping" sort="Ding, Xiuping" uniqKey="Ding X" first="Xiuping" last="Ding">Xiuping Ding</name><name sortKey="Fan, Liyuan" sort="Fan, Liyuan" uniqKey="Fan L" first="Liyuan" last="Fan">Liyuan Fan</name><name sortKey="Li, Baosheng" sort="Li, Baosheng" uniqKey="Li B" first="Baosheng" last="Li">Baosheng Li</name><name sortKey="Li, Baosheng" sort="Li, Baosheng" uniqKey="Li B" first="Baosheng" last="Li">Baosheng Li</name><name sortKey="Wang, Juan" sort="Wang, Juan" uniqKey="Wang J" first="Juan" last="Wang">Juan Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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