MiR-99a Enhances the Radiation Sensitivity of Non-Small Cell Lung Cancer by Targeting mTOR
| العنوان: | MiR-99a Enhances the Radiation Sensitivity of Non-Small Cell Lung Cancer by Targeting mTOR |
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| المؤلفون: | Hongyu Ma, Siliang Zhang, Yu Zhang, Shiqi Piao, Yang Li, Qingyong Xu, Yuanyuan Qu, Hang Yin, Jianqun Ma, Xiaoyuan Wang, Lin Chen |
| المصدر: | Cellular Physiology and Biochemistry, Vol 46, Iss 2, Pp 471-481 (2018) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Lung Neoplasms, Physiology, Cell Survival, Morpholines, Transplantation, Heterologous, Microrna-99a, non-small cell lung cancer (NSCLC), Down-Regulation, Mice, Nude, Non-small cell lung cancer (NSCLC), Biology, Radiation Tolerance, lcsh:Physiology, Radiosensitivity, lcsh:Biochemistry, 03 medical and health sciences, Mice, 0302 clinical medicine, Radiation sensitivity, Radioresistance, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, microRNA, Databases, Genetic, medicine, Animals, Humans, lcsh:QD415-436, 3' Untranslated Regions, Mammalian target of rapamycin (mTOR), PI3K/AKT/mTOR pathway, lcsh:QP1-981, TOR Serine-Threonine Kinases, Cancer, Antagomirs, Cell Cycle Checkpoints, Cell cycle, medicine.disease, MicroRNAs, 030104 developmental biology, Pyrimidines, A549 Cells, Gamma Rays, 030220 oncology & carcinogenesis, Benzamides, Cancer research, Signal Transduction |
| الوصف: | Background/Aims: Radiation therapy is an important and effective modality for the treatment of non-small cell lung cancer (NSCLC). MicroRNAs (miRNAs) are crucial post-transcriptional regulators that are involved in numerous important biologic processes. However, their potential involvement in radiation sensitivity remains unknown. Materials: We performed integrated analysis of miRNA expression in NSCLC using The Cancer Genome Atlas datasets. miR-99a was found to be significantly upregulated in cancer tissue and regulated cell survival. Cell culture was used to assess the role of miR-99a in radiation sensitivity. We then used flow cytometry to examine the effects of miR-99a on the cell cycle and apoptosis in cells exposed to radiation. To identify gene targets of miR-99a, a bioinformatics approach was adopted, and the findings of this analysis were verified using luciferase reporter assays. Finally, an in vivo study was conducted to examine the effect of miR-99a on tumor volume in an NSCLC mouse model undergoing radiation therapy. Results: miR-99a was significantly upregulated in radiation-sensitive A549 cells compared with radiation-resistant A549 cells. miR-99a overexpression was shown to enhance radiosensitivity, while inhibition of miR-99a resulted in radioresistance of NSCLC cell lines in vitro and in vivo. In addition, by bioinformatics software analysis and luciferase assays, mammalian target of rapamycin (mTOR) was identified as a direct target of miR-99a. Furthermore, AZD2014, an inhibitor of mTOR, enhanced radiosensitivity and apoptosis in NSCLC cell lines, while mTOR overexpression resulted in radioresistance and cell survival from miR-99a-induced cell apoptosis. Moreover, miR-99a overexpression further increased the efficacy of radiation therapy in an NSCLC xenograft mouse model, and miR-99a and mTOR expression was significantly inversely correlated. Conclusions: Altogether, these data suggested miR-99a functions as a tumor suppressor that has a critical role in regulating radiosensitivity of NSCLC by targeting the mTOR signaling pathway. |
| اللغة: | English |
| تدمد: | 1421-9778 1015-8987 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53be94ad7e3019795f1b1f49f0cc75c1Test https://www.karger.com/Article/FullText/488615Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....53be94ad7e3019795f1b1f49f0cc75c1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14219778 10158987 |
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