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

• Published in: Cell death & disease 2019-02, Vol.10 (3), p.150-150, Article 150
• Main Authors: Shi, Liangliang, Hong, Xiaohua, Ba, Li, He, Xiaoxiao, Xiong, Yin, Ding, Qian, Yang, Shengli, Peng, Gang
• Format: Article
• Language: English
• Subjects: 13/89; 631/67/1504/1885; 631/67/322; 82/51; 96/1; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Carcinogenesis - genetics; Cell Biology; Cell Culture; Cell proliferation; Cell Proliferation - genetics; Cell Survival - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Disease Progression; DNA microarrays; Enhancer of Zeste Homolog 2 Protein - genetics; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic - genetics; Gene Knockdown Techniques; HEK293 Cells; Heterografts; HT29 Cells; Humans; Immunology; Kinases; Life Sciences; Male; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; Middle Aged; Neoplasm Metastasis - genetics; Non-coding RNA; Phenotypes; Polycomb group proteins; RNA, Long Noncoding - genetics; Therapeutic applications; Transduction, Genetic; Transfection; Tumorigenesis
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1332-8

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.