Aberrant miR-1246 expression promotes radioresistance in non-small cell lung cancer: a potential prognostic biomarker and radiotherapy sensitization target
Identifieur interne : 000225 ( Main/Exploration ); précédent : 000224; suivant : 000226Aberrant 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.
Url:
PubMed: 32064170
PubMed Central: 7017745
Affiliations:
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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><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 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250117</wicri:regionArea></affiliation></author><author><name sortKey="Li, Baosheng" sort="Li, Baosheng" uniqKey="Li B" first="Baosheng" last="Li">Baosheng Li</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><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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