miR‑223 functions as a potent tumor suppressor of the Lewis lung carcinoma cell line by targeting insulin‑like growth factor‑1 receptor and cyclin-dependent kinase 2

Nian,Weiqi; Ao,Xujun; Wu,Yongzhong; Huang,Yi; Shao,Jianghe; Wang,Yiming; Chen,Zhengtang; Chen,Fanglin; Wang,Donglin

doi:10.3892/ol.2013.1375

miR‑223 functions as a potent tumor suppressor of the Lewis lung carcinoma cell line by targeting insulin‑like growth factor‑1 receptor and cyclin-dependent kinase 2

Authors:
- Weiqi Nian
- Xujun Ao
- Yongzhong Wu
- Yi Huang
- Jianghe Shao
- Yiming Wang
- Zhengtang Chen
- Fanglin Chen
- Donglin Wang
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Affiliations: Department of Oncology, Chongqing Tumor Hospital, Chongqing 400030, P.R. China, Institute of Cancer Research, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China, Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, P.R. China
Published online on: June 4, 2013 https://doi.org/10.3892/ol.2013.1375
Pages: 359-366

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Abstract

microRNAs (miRNAs) have been hypothesized to function as oncogenes or tumor suppressors by targeting specific cancer‑related genes. Previous studies have reported that miR‑223 may serve as a tumor suppressor in a number of cancer types, however, knowledge of its targets in non‑small cell lung cancer (NSCLC) remains limited. In the current study, miR‑223 was found to inhibit cell proliferation in vitro by CCK‑8 assay, growth curves and an anchorage‑independent growth assay in a Lewis lung carcinoma (LLC) cell line. miR‑223 transfection in the LLC cells was observed to significantly inhibit migration and invasion, induce G2/M arrest and decrease the expression levels of Sca‑1, a marker of murine stem cells. In addition, miR‑223 transfection markedly suppressed AKT and ERK signaling, as well as insulin‑like growth factor‑1 receptor (IGF‑1R)‑mediated downstream signaling, pathways that are crucial for cell proliferation and invasion in NSCLC cells. Analyses in C57BL/6 mice demonstrated that miR‑223 suppresses tumorigenicity in vivo. Using a luciferase activity assay and western blot analysis, IGF‑1R and cyclin-dependent kinase 2 (CDK2) were identified as direct targets of miR‑223. In the present study, novel cancer‑related targets of miR‑223 were identified and verified in a LLC cell line, indicating that miR‑223 functions as a tumor suppressor, which may fine‑tune the activity of the IGF‑1R pathway in lung cancer. Therefore, increasing miR‑223 expression may provide a novel approach for the treatment of NSCLC.

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