Long non-coding RNA AK001058 regulates tumor growth and angiogenesis in colorectal cancer via methylation of ADAMTS12.

Abstract:

:Colorectal cancer, a common gastrointestinal malignant tumor, has been a leading cause of cancer related deaths. Long non-coding RNAs (lncRNAs) play an important role in regulating cancer development. The aim of this study was to investigate the role and potential mechanism of lncRNA AK001058 in colorectal cancer. To establish tumor xenografts, BALB/c nude mice received subcutaneously injection of SW480 cells with transfection targeting AK001058 (overexpression or knockdown). Tumor growth was observed and recorded. The relative gene expression levels were determined by quantitative real-time PCR or western blot. Cell apoptosis was determined by tunnel analysis. Microvessel morphology changes were detected by H&E staining. Methylation level of CpG island was analyzed using methylation specific PCR. The results showed that AK001058 overexpression notably accelerated tumor growth. AK001058 overexpression also decreased cell apoptosis, worsened microvessel morphology and increased the expression of VEGFA and angiopoietin II. Moreover, AK001058 decreased the expression of ADAMTS12 by increasing its methylation level. Nevertheless, AK001058 knockdown exerted the opposite function. Therefore, AK001058 knockdown could effectively inhibit tumor growth mostly accounting for decreased cell apoptosis and tumor angiogenesis, which was partly dependent on the high methylation level of ADATS12. These data provided a novel therapeutic strategy of colorectal cancer.

journal_name

Am J Transl Res

authors

Zheng S,Lin F,Zhang M,Mu N,Ge X,Fu J

subject

Has Abstract

pub_date

2019-09-15 00:00:00

pages

6117-6123

issue

9

issn

1943-8141

journal_volume

11

pub_type

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