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

Abstract

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.

Keywords: AFAP1-AS1; HBP1; LSD1; long noncoding RNA; non-small-cell lung cancer.