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

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.

• Publication year

  2013

• Venue

  Oncology Letters

• Publication date

  2013-06-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3892/ol.2013.1375PMID 24137330PMCID 3789020
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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