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

Overview

Journal Oncol Lett

Specialty Oncology

Date 2013 Oct 19

PMID 24137330

Citations 37

Authors

Weiqi Nian

Xujun Ao

Yongzhong Wu

Yi Huang

Jianghe Shao

Yiming Wang

Zhengtang Chen

Fanglin Chen

Donglin Wang

Affiliations

Soon will be listed here.

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 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 G/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 . 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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