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

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

Received 21 November 2017

Accepted for publication 18 January 2018

Published 26 March 2018 Volume 2018:11 Pages 1721—1732


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza

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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