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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.

SUBMITTER: Yu S

PROVIDER: S-EPMC6609801 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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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.

Yu Shanxun S Yang Daolu D Ye Yunyao Y Liu Pei P Chen Zhenyao Z Lei Tianyao T Pu Jiaze J Liu Longfa L Wang Zhaoxia Z

Cancer science 20190529 7

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 demeth ...[more]

PMID: 31069893

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Project description:Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4-AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4-AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4-AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4-AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4-AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221-3.760). In this study, a genome-wide RNA sequencing dataset was used to identify 927 genes co-expressing with FOXP4-AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4-AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome-wide RNA sequencing dataset was done. We have found that FOXP4-AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor-related pathways such as NF-kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4-AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4-AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome-wide approaches, we identified the potential molecular mechanisms of FOXP4-AS1 in PDAC and two targeted therapeutic drugs for it.

Dataset Information

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.

Publications

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.

Similar Datasets

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