West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. Asian Pacific Journal of Cancer Prevention 1513-7368 14 1 2013 01 01 Let-7c Inhibits NSCLC Cell Proliferation by Targeting HOXA1 387 392 27336 EN Journal Article 1970 01 01 <br/><b>Objective</b>: The aim of the present study was to explore mechanisms by which let-7c suppresses NSCLC cellproliferation. <br/><b>Methods</b>: The expression level of let-7c was quantified by qRT-PCR. A549 and H1299 cells weretransfected with let-7c mimics to restore the expression of let-7c. The effects of let-7c were then assessed by cellproliferation, colony formation and cell cycle assay. Mouse experiments were used to confirm the effect of let-7con tumorigenicity in vivo. Luciferase reporter assays and Western blotting were performed to identify targetgenes for let-7c. <br/><b>Results</b>: HOXA1 was identified as a novel target of let-7c. MTS, colony formation and flowcytometry assays demonstrated that forced expression of let-7c inhibited NSCLC cell proliferation by inducingG1 arrest in vitro, consistent with inhibitory effects induced by knockdown of HOXA1. Mouse experimentsdemonstrated that let-7c expression suppressed tumorigenesis. Furthermore, we found that let-7c could regulatethe expression of HOXA1 downstream effectors CCND1, CDC25A and CDK2. <br/><b>Conclusions</b>: Collectively, theseresults demonstrate let-7c inhibits NSCLC cell proliferation and tumorigenesis by partial direct targeting ofthe HOXA1 pathway, which suggests that restoration of let-7c expression may thus offer a potential therapeuticintervention strategy for NSCLC. https://journal.waocp.org/article_27336_9b8e5279f2ca3fcdb18c34a313340678.pdf