miR-198-induced upregulation of Livin may be associated with the prognosis and contribute to the oncogenesis of lung adenocarcinoma

Liang,Yicheng; Wang,Hetan; Sun,Yuanyuan; Chen,Sheng; Wang,Haoyou; Huang,Rong; Zhao,Xinyi; Fu,Weineng; Yang,Chunlu

doi:10.3892/or.2017.5866

miR-198-induced upregulation of Livin may be associated with the prognosis and contribute to the oncogenesis of lung adenocarcinoma

Authors:
- Yicheng Liang
- Hetan Wang
- Yuanyuan Sun
- Sheng Chen
- Haoyou Wang
- Rong Huang
- Xinyi Zhao
- Weineng Fu
- Chunlu Yang
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Affiliations: Department of Thoracic Surgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Medical Genetics, China Medical University, Shenyang, Liaoning 110001, P.R. China, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China
Published online on: August 1, 2017 https://doi.org/10.3892/or.2017.5866
Pages: 2096-2104
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Livin, a member of the inhibitor of apoptosis protein (IAP) family, is expressed at a high level in lung adenocarcinoma and influences the progression of cancer, and its response to chemotherapy and radiotherapy. Aberrant microRNA (miRNA) expression has also been associated with cancer initiation and development. However, the clinical significance of Livin and its relationship with miRNAs in lung adenocarcinoma are still unclear. In the present study, the expression level of Livin in 90 pairs of lung adenocarcinoma and their adjacent tissues were detected by immunohistochemistry staining. Spearman correlation and Kaplan-Meier, univariate and multivariate analyses were applied to evaluate the correlation between the expression of Livin and clinical characteristics. With the integration of bioinformatics analysis and dual-luciferase reporter gene assays, we identified the miRNA that can target Livin mRNA. The functional effects of miRNA-mediated Livin knockdown were assessed by Cell Counting Kit-8 (CCK-8) and apoptosis assays, and cell cycle analysis. The present study revealed that Livin was upregulated in lung adenocarcinoma tissues and may be associated with the poor prognosis in lung adenocarcinoma patients. The overexpression of Livin is partly caused by the downregulation of miR-198. Further exploration revealed that miRNA-198-mediated silencing of Livin significantly inhibited cell growth and enhanced apoptosis of A549 cells, accompanied by marked upregulation of caspase-3. Finally, we observed that the miR-198 overexpression and Livin neutralization had similar effects on improving cisplatin chemosensitivity in A549 cells. Overall, these findings suggest that Livin has the potential to become a biomarker for predicting the prognosis of lung adenocarcinoma and may provide a promising strategy for assisting chemotherapy of lung adenocarcinoma through the miR-198/Livin/caspase-3 regulatory network.

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