Long non-coding RNA ZNFX1-AS1 promotes the tumor progression and metastasis of colorectal cancer by acting as a competing endogenous RNA of miR-144 to regulate EZH2 expression

Liangliang Shi,Xiaohua Hong,Shengli Yang,Li Ba,Yin Xiong,Xiaoxiao He,Qian Ding,Gang Peng

doi:10.1038/s41419-019-1332-8

Abstract

Mounting evidences indicated that long non-coding RNA is dysregulated and involved in the pathology of tumors. However, the role of lncRNAs in colorectal cancer (CRC) progression is not fully determined. Differentially expressed lncRNA profile in CRC was conducted by lncRNA microarray in 15 pairs of CRC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 106 pairs of tissues. The biological effect of lncRNA ZNFX1-AS1 was evaluated by in vitro and in vivo assays. The regulation between lncRNA ZNFX1-AS1 and miR-144 was evaluated by a series of experiments. We found that lncRNA ZNFX1-AS1 expression was significantly upregulated in CRC tissues and cell lines, and the expression of lncRNA ZNFX1-AS1 was associated with aggressive tumor phenotype and poor prognosis in CRC. Functionally, knockdown of lncRNA ZNFX1-AS1 inhibited cell proliferation, invasion, in vitro and tumorigenesis and metastasis in vivo. Further investigation demonstrated that lncRNA ZNFX1-AS1 functioned as a competing endogenous RNA (ceRNA) for miR-144, thereby leading to the depression of its endogenous target gene Polycomb group protein enhancer of zeste homolog 2 (EZH2). We found that lncRNA ZNFX1-AS1 is significantly upregulated in CRC, and the newly identified lncRNA ZNFX1-AS1-miR-144-EZH2 axis is involved in the regulation of CRC progression, which might be used as potential therapeutic targets for CRC patients.

Highlights

In recent years, integrative genomic and transcriptome sequencing have indicated that more than 90% of the DNA sequence is actively transcribed, with 98% of these genomes transcribed into non-coding RNAs, including microRNAs and long ncRNAs[1,2]
To confirm the microarray results, we randomly selected the top 10 lncRNAs that were upregulated in Colorectal cancer (CRC) for validation using real-time PCR analysis, the results showed that 6 of these lncRNAs were upregulated in CRC tissues compared with adjacent normal tissues
The results showed that only lncRNA ZNFX1-AS1 (Accession: NR_003604, a 1008 bp transcript, locates in chromosome 20q13.13) was significantly overexpressed in CRC tissues (Fig. 1a)

Summary

Introduction

Integrative genomic and transcriptome sequencing have indicated that more than 90% of the DNA sequence is actively transcribed, with 98% of these genomes transcribed into non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long ncRNAs (lnRNAs)[1,2]. Among these ncRNAs, miRNAs have been widely studied and found to be involved in the regulation of biological behaviors of cancer cells such as cell proliferation, cell. It is compelling needed to seek out the molecular that drive CRC metastasis and progression and illuminate its underlying mechanisms

Methods

Results

Conclusion