OncoTargets and Therapy (Mar 2018)

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

  • Bao M,
  • Song YJ,
  • Xia JJ,
  • Li PL,
  • Liu Q,
  • Wan ZR

Journal volume & issue
Vol. Volume 11
pp. 1721 – 1732

Abstract

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Min Bao, Yingjian Song, Jingjing Xia, Pengling Li, Qing Liu, Zongren Wan Department of Pneumology, Huai’an First People’s Hospital, Huai’an, China Background and aim: 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. Methods and results: 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. Conclusion: These results demonstrate that miR-1269 promotes cell survival and proliferation by targeting TP53 and caspase-9 in lung cancer. Keywords: microRNA-1269, tumor protein p53, caspase, cell apoptosis, lung carcinoma

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