miR‑505 inhibits cell growth and EMT by targeting MAP3K3 through the AKT‑NFκB pathway in NSCLC cells

Tang,Huaping; Lv,Weihong; Sun,Wenxin; Bi,Qiaojie; Hao,Yueqin

doi:10.3892/ijmm.2018.4041

miR‑505 inhibits cell growth and EMT by targeting MAP3K3 through the AKT‑NFκB pathway in NSCLC cells

Authors:
- Huaping Tang
- Weihong Lv
- Wenxin Sun
- Qiaojie Bi
- Yueqin Hao
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Affiliations: Department of Respiration, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China, Department of Medical, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China, Department of Emergency, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China
Published online on: December 31, 2018 https://doi.org/10.3892/ijmm.2018.4041
Pages: 1203-1216
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs) are short non‑coding RNAs, which generally regulate gene expression at the post‑transcriptional level. Dysregulation of miRNAs has been reported in numerous cancer types, including lung cancer. In the present study, the role of miR‑505 in non‑small cell lung cancer (NSCLC) cells was investigated. miR‑505 served a tumor suppressor role in NSCLC cells. By reverse transcriptase‑quantitative polymerase chain reaction detection, it was demonstrated that miR‑505 was downregulated in NSCLC tissues and cell lines, which is negatively associated with large tumor size, Tumor‑Node‑Metastasis stage and distant metastasis in patients with NSCLC. Functional studies revealed that miR‑505 inhibited cell proliferation, migration, invasion and epithelial‑mesenchymal transition progress in vitro and tumor growth in vivo. Mechanically, mitogen‑activated protein kinase kinase kinase 3 (MAP3K3) was identified as a direct target of miR‑505 by binding to its 3'untranslated region and demonstrated to mediate the tumor suppressor roles of miR‑505 in NSCLC cells. The effect of miR‑505 on the activation of AKT/nuclear factor‑κB (NFκB) pathway, which was downstream targets of MAP3K3, was further analyzed by western blot analysis and immunofluorescence analyses. The data demonstrated the inhibition of the AKT/NFκB pathway upon overexpressing miR‑505 and the activation of AKT/NFκB pathway upon silencing miR‑505. Collectively, the data revealed the novel role and target of miR‑505 in NSCLC cells, which may provide novel insights regarding its role in the carcinogenesis of NSCLC and its potential values for clinical applications.

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