Open AccessLong 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
Author(s) -
Yu Shanxun,
Yang Daolu,
Ye Yunyao,
Liu Pei,
Chen Zhenyao,
Lei Tianyao,
Pu Jiaze,
Liu Longfa,
Wang Zhaoxia
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14039
Subject(s) - antisense rna , gene knockdown , biology , microbiology and biotechnology , rna , demethylase , cancer research , carcinogenesis , long non coding rna , downregulation and upregulation , gene silencing , non coding rna , rna binding protein , epigenetics , chemistry , cell culture , cancer , gene , biochemistry , genetics
The number of documented long noncoding RNA s (lnc RNA s) 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 ( AFAP 1‐ AS 1) is a 6810‐nt lnc RNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP 1‐ AS 1, recruiting and binding to lysine‐specific demethylase 1 ( LSD 1), was generally overexpressed in human non‐small‐cell lung cancer ( NSCLC ) tissues using quantitative real‐time PCR . Higher AFAP 1‐ AS 1 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 AFAP 1‐ AS 1 downregulation inhibited cell migration and induced apoptosis; AFAP 1‐ AS 1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP 1‐ AS 1 repressed HMG box‐containing protein 1 ( HBP 1) expression by recruiting LSD 1 to the HBP 1 promoter regions in PC ‐9 and H1975 cells. Furthermore, HBP 1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP 1‐ AS 1 is partially dependent on the epigenetic silencing of HBP 1. In conclusion, our results indicate that AFAP 1‐ AS 1 is carcinogenic and that the AFAP 1‐ AS 1/ LSD 1/ HBP 1 axis could constitute a new therapeutic direction for NSCLC .