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Let-7c Inhibits NSCLC Cell Proliferation by Targeting HOXA1

  • Zhan, Min (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University) ;
  • Qu, Qiang (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University) ;
  • Wang, Guo (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University) ;
  • Liu, Ying-Zi (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University) ;
  • Tan, Sheng-Lan (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University) ;
  • Lou, Xiao-Ya (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University) ;
  • Yu, Jing (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University) ;
  • Zhou, Hong-Hao (Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University)
  • Published : 2013.01.31

Abstract

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.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China

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