| Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. | |
| | |
MedLine Citation:
|
PMID: 22469983 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
MicroRNAs (miRNAs) act as important gene regulators in human genomes and their aberrant expression links to many malignancies. We previously identified a different characteristic miRNA expression profile in cervical cancer from that in cervical normal tissues, including the downregulated miR-424. However, the role and mechanism of miR-424 in cervical cancer still remain unknown. Here, we focused on identifying the tumor-suppressive function and clinical significance of miR-424 and exploring the mechanistic relevance by characterizing its target. We showed a significantly decreased expression of miR-424 in 147 cervical cancer tissues versus 74 cervical normal tissues by performing quantitative RT-PCR. In 147 cervical cancer tissue samples, low-level expression of miR-424 was positively correlated with poor tumor differentiation, advanced clinical stage, lymph node metastasis and other poor prognostic clinicopathological parameters. Further in vitro observations showed that enforced expression of miR-424 inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, and suppressed cell migration and invasion in two human cervical cancer cell lines, SiHa and CaSki, implying that miR-424 functions as a tumor suppressor in the progression of cervical cancer. Interestingly, overexpression of miR-424 inhibited the expression of protein checkpoint kinase 1 (Chk1) and phosphorylated Chk1 (p-Chk1) at residues Ser345 and decreased the activity of luciferase-reporter containing the 3'-untranslated region (UTR) of Chk1 with predicted miR-424-binding site. Moreover, miR-424 expression levels were inversely correlated with Chk1 and p-Chk1 protein levels in both cervical cancer and normal tissues. Furthermore, RNAi-mediated knockdown of Chk1 decreased matrix metalloproteinase 9 expression and phenocopied the tumor suppressive effects of miR-424 in cell models. Taken together, our results identify a crucial tumor suppressive role of miR-424 in the progression of cervical cancer at least partly via upreglating the expression of Chk1 and p-Chk1, and suggest that miR-424 might be a candidate of prognostic predictor or an anticancer therapeutic target for cervical cancer patients.Oncogene advance online publication, 2 April 2012; doi:10.1038/onc.2012.121. |
| | |
Authors:
|
J Xu; Y Li; F Wang; X Wang; B Cheng; F Ye; X Xie; C Zhou; W Lu |
Related Documents
:
|
22820863 - Conditionally replicative adenovirus-based mda-7/il-24 expression enhances sensitivity ... 21491053 - Analysis of the paracrine loop between cancer cells and fibroblasts using a microfluidi... 18364263 - An investigation of the differential expression of her2/neu gene expression in normal o... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-4-02 |
Journal Detail:
|
Title: Oncogene Volume: - ISSN: 1476-5594 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
|
Created Date: 2012-4-3 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8711562 Medline TA: Oncogene Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Role of Lefty in the anti tumor activity of human adult liver stem cells.
Next Document: The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acut...