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Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer.

ABSTRACT: Increasing evidences have shown that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. However, the contributions of lncRNAs to colorectal cancer remain largely unknown. Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment.

SUBMITTER: Tang J

PROVIDER: S-EPMC5992508 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer.

Tang Jianming J Zhong Guansheng G Wu Jianhui J Chen Haiyan H Jia Yongshi Y

American journal of cancer research 20180501 5

Increasing evidences have shown that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. However, the contributions of lncRNAs to colorectal cancer remain largely unknown. Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model syst ...[more]

PMID: 29888110

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Project description:BackgroundLong noncoding RNA (lncRNA) can regulate various physiological and pathological processes through multiple molecular mechanisms in cis and in trans. However, the role of lncRNAs in cardiac hypertrophy is yet to be fully elucidated.MethodsA mouse lncRNA microarray was used to identify differentially expressed lncRNAs in the mouse hearts following transverse aortic constriction-induced pressure overload comparing to the sham-operated samples. The direct impact of one lncRNA, Ahit, on cardiomyocyte hypertrophy was characterized in neonatal rat cardiomyocytes in response to phenylephrine by targeted knockdown and overexpression. The in vivo function of Ahit was analyzed in mouse hearts by using cardiac-specific adeno-associated virus, serotype 9-short hairpin RNA to knockdown Ahit in combination with transverse aortic constriction. Using catRAPID program, an interaction between Ahit and SUZ12 (suppressor of zeste 12 protein homolog) was predicted and validated by RNA immunoprecipitation and immunoblotting following RNA pull-down. Chromatin immunoprecipitation was performed to determine SUZ12 or H3K27me3 occupancy on the MEF2A (myocyte enhancer factor 2A) promoter. Finally, the expression of human Ahit (leukemia-associated noncoding IGF1R activator RNA 1 [LUNAR1]) in the serum samples from patients of hypertrophic cardiomyopathy was tested by quantitative real-time polymerase chain reaction.ResultsA previously unannotated lncRNA, antihypertrophic interrelated transcript (Ahit), was identified to be upregulated in the mouse hearts after transverse aortic constriction. Inhibition of Ahit induced cardiac hypertrophy, both in vitro and in vivo, associated with increased expression of MEF2A, a critical transcriptional factor involved in cardiac hypertrophy. In contrast, overexpression of Ahit significantly attenuated stress-induced cardiac hypertrophy in vitro. Furthermore, Ahit was significantly upregulated in serum samples of patients diagnosed with hypertensive heart disease versus nonhypertrophic hearts (1.46±0.17 fold, P=0.0325). Mechanistically, Ahit directly bound and recruited SUZ12, a core PRC2 (polycomb repressive complex 2) protein, to the promoter of MEF2A, triggering its trimethylation on H3 lysine 27 (H3K27me3) residues and mediating the downregulation of MEF2A, thereby preventing cardiac hypertrophy.ConclusionsAhit is a lncRNA with a significant role in cardiac hypertrophy regulation through epigenomic modulation. Ahit is a potential therapeutic target of cardiac hypertrophy.

Dataset Information

Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer.

Publications

Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer.

Similar Datasets

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