miR-144-5p Enhances the Radiosensitivity of Non-Small-Cell Lung Cancer Cells via Targeting ATF2

• Published in: BioMed research international 2018-01, Vol.2018 (2018), p.1-10
• Main Authors: Li, Dan, Wang, Ying, Jie, Jing, Ma, Lianjun, Li, Xiaoping, Hua, Shucheng, Chen, Wei, Song, Lei, Chen, Dong
• Format: Article
• Language: English
• Subjects: Activating transcription factor 2; Activating Transcription Factor 2 - genetics; Activating Transcription Factor 2 - metabolism; Animals; Apoptosis; Apoptosis - genetics; Apoptosis - radiation effects; Base Sequence; Bioinformatics; Biological activity; Cancer; Cancer cells; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell culture; Cell differentiation; Cell growth; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Survival - genetics; Cell Survival - radiation effects; Deregulation; Differentiation (biology); Gene expression; Gene Expression Regulation, Neoplastic - radiation effects; Health aspects; Humans; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical prognosis; Metastases; Mice, Inbred BALB C; Mice, Nude; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Non-small cell lung carcinoma; Oncology; Post-transcription; Radiation; Radiation therapy; Radiation Tolerance - genetics; Radiation Tolerance - radiation effects; Radiation, Ionizing; Radiosensitivity; Restoration; Stem cells; Therapeutic applications; Transcription factors; Xenografts; Xenotransplantation
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2018/5109497

MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells in vitro and A549 cell mouse xenografts in vivo. Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation in vitro and in vivo. Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC.