title: Let-7c inhibits NSCLC cell proliferation by targeting HOXA1.
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.
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qu
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Liu
authors.forename: Sheng-Lan
authors.initials: SL
authors.lastname: Tan
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Lou
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014410:Tumor Stem Cell Assay; D020687:cdc25 Phosphatases / Q000378:metabolism; D000099261:Homeobox A1 Protein
chemical_list: D020413:3' Untranslated Regions; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D020687:cdc25 Phosphatases; D000099261:Homeobox A1 Protein; C530104:CCND1 protein, human; C487931:mirnlet7 microRNA, human; C495894:CDK2 protein, human; C517004:CDC25A protein, human