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Let-7c Inhibits NSCLC Cell Proliferation by Targeting HOXA1.
MedLine Citation:
PMID:  23534758     Owner:  NLM     Status:  In-Data-Review    
Objective: The aim of the present study was to explore mechanisms by which let-7c suppresses NSCLC cell proliferation. Methods: The expression level of let-7c was quantified by qRT-PCR. A549 and H1299 cells were transfected with let-7c mimics to restore the expression of let-7c. The effects of let-7c were then assessed by cell proliferation, colony formation and cell cycle assay. Mouse experiments were used to confirm the effect of let-7c on tumorigenicity in vivo. Luciferase reporter assays and Western blotting were performed to identify target genes for let-7c. Results: HOXA1 was identified as a novel target of let-7c. MTS, colony formation and flow cytometry assays demonstrated that forced expression of let-7c inhibited NSCLC cell proliferation by inducing G1 arrest in vitro, consistent with inhibitory effects induced by knockdown of HOXA1. Mouse experiments demonstrated that let-7c expression suppressed tumorigenesis. Furthermore, we found that let-7c could regulate the expression of HOXA1 downstream effectors CCND1, CDC25A and CDK2. Conclusions: Collectively, these results demonstrate let-7c inhibits NSCLC cell proliferation and tumorigenesis by partial direct targeting of the HOXA1 pathway, which suggests that restoration of let-7c expression may thus offer a potential therapeutic intervention strategy for NSCLC.
Min Zhan; Qiang Qu; Guo Wang; Ying-Zi Liu; Sheng-Lan Tan; Xiao-Ya Lou; Jing Yu; Hong-Hao Zhou
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Asian Pacific journal of cancer prevention : APJCP     Volume:  14     ISSN:  1513-7368     ISO Abbreviation:  Asian Pac. J. Cancer Prev.     Publication Date:  2013  
Date Detail:
Created Date:  2013-03-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130625     Medline TA:  Asian Pac J Cancer Prev     Country:  Thailand    
Other Details:
Languages:  eng     Pagination:  387-92     Citation Subset:  IM    
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China E-mail :
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