title: 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.
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 proliferationin vitroby 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 tumorigenicityin 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.
authors.affiliation: 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.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Nian
authors.forename: Xujun
authors.initials: X
authors.lastname: Ao
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Jianghe
authors.initials: J
authors.lastname: Shao
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhengtang
authors.initials: Z
authors.lastname: Chen
authors.forename: Fanglin
authors.initials: F
authors.lastname: Chen
authors.forename: Donglin
authors.initials: D
authors.lastname: Wang
keywords: metastasis; miR-223; non-small cell lung cancer; self-renewal; tumor suppressor