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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.
| Content Provider | Europe PMC |
|---|---|
| Author | NIAN, WEIQI AO, XUJUN WU, YONGZHONG HUANG, YI SHAO, JIANGHE WANG, YIMING CHEN, ZHENGTANG CHEN, FANGLIN WANG, DONGLIN |
| Copyright Year | 2013 |
| 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. |
| ISSN | 17921074 |
| Journal | Oncology Letters |
| Volume Number | 6 |
| PubMed Central reference number | PMC3789020 |
| Issue Number | 2 |
| PubMed reference number | 24137330 |
| e-ISSN | 17921082 |
| DOI | 10.3892/ol.2013.1375 |
| Language | English |
| Publisher | D.A. Spandidos |
| Publisher Date | 2013-06-04 |
| Access Restriction | Open |
| Rights License | This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. Copyright © 2013, Spandidos Publications |
| Subject Keyword | non-small cell lung cancer miR-223 tumor suppressor metastasis self-renewal |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |