Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer

: The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) is a 6810-nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP1-AS1, recruiting and binding to lysine-specific demethylase 1 (LSD1), was generally overexpressed in human non-small-cell lung cancer (NSCLC) tissues using quantitative real-time PCR. Higher AFAP1-AS1 expression was significantly correlated with larger tumor size (P = .008), lymph node metastasis (P = .025), higher TNM stage (P = .024), and worse overall survival in NSCLC patients. In vitro experiments revealed that AFAP1-AS1 downregulation inhibited cell migration and induced apoptosis; AFAP1-AS1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP1-AS1 repressed HMG box-containing protein 1 (HBP1) expression by recruiting LSD1 to the HBP1 promoter regions in PC-9 and H1975 cells. Furthermore, HBP1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP1-AS1 is partially dependent on the epigenetic silencing of HBP1. In conclusion, our results indicate that AFAP1-AS1 is carcinogenic and that the AFAP1-AS1/LSD1/HBP1 axis could constitute a new therapeutic direction for NSCLC.