miR-1269 promotes cell survival and proliferation by targeting tp53 and caspase-9 in lung cancer

• Published in: OncoTargets and therapy Vol. 11; pp. 1721 - 1732
• Main Authors: Bao, Min, Song, Yingjian, Xia, Jingjing, Li, Pengling, Liu, Qing, Wan, Zongren
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Analysis; Apoptosis; Binding sites; Cancer genetics; Cancer metastasis; Carcinoma; caspase; cell apoptosis; Cell growth; Cholecystokinin; Cyclin-dependent kinases; Death; Gene expression; Genes; Genetic aspects; Genetic engineering; Genomes; Genomics; Health aspects; Immunohistochemistry; Kinases; Luciferase; Lung cancer; lung carcinoma; Medical prognosis; Metastasis; MicroRNA; microRNA-1269; MicroRNAs; Original Research; Proteins; Studies; tumor protein p53; Tumor proteins; Tumors; United States > US; China; cell apoptosis; microRNA-1269; lung carcinoma; tumor protein p53; caspase
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S157715

Lung cancer is the leading cause of cancer death worldwide. In this study, we aim to elucidate the role of miR-1269 in the pathogenesis of lung cancer. From the results of analyses using The Cancer Genome Atlas (TCGA) database, we noted the expression of miR-1269 was increased in lung cancer tissue. miR-1269 expression was detected in both the normal adjacent lung tissue and in the tumorous lung tissue of lung cancer patients, and miR-1269 was more highly expressed in the tumors. High expression of miR-1269 correlated with patients' tumor stage and lymph node metastasis. A Cell Counting Kit-8 (CCK8) analysis and a cloning formation assay showed that overexpression of miR-1269 significantly promoted the growth of A549 cells, and that a lower expression of miR-1269 significantly increased cell apoptosis. We used the TargetScan 6.2 Database to predict the potential targets of miR-1269, and a luciferase activity assay was used to determine the direct interaction between miR-1269, tumor protein p53 (TP53), and caspase-9. Results from Western blots and real-time PCR showed that overexpression of miR-1269 significantly inhibited TP53 and caspase-9 expression. In addition, caspase-3 activity was found to decrease in a miR-1269 mimic group. The results showed that gene silencing of TP53 and caspase-9 significantly inhibited A549 cell growth and promoted cell apoptosis. The results also showed that the inhibition of miR-1269 and caspase-9 expression inhibited cell apoptosis. Immunohistochemistry (IHC) results demonstrated that TP53 and caspase-9 were expressed in low levels in tumor tissues, and that an inverse correlation exists between miR-1269 expression levels and TP53 or caspase-9 expression levels. These results demonstrate that miR-1269 promotes cell survival and proliferation by targeting TP53 and caspase-9 in lung cancer.