Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cell Death Dis. 2019 Feb 15;10(3):150. 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.
越来越多的证据表明,长非编码 RNA 失调并参与肿瘤的病理学。然而,lncRNAs 在结直肠癌(CRC)进展中的作用尚未完全确定。通过对 15 对 CRC 组织和相邻正常组织进行 lncRNA 微阵列分析,检测 CRC 中差异表达的 lncRNA 图谱,并通过对另外 106 对组织的实时 PCR 分析进行验证。通过体外和体内实验评估 lncRNA ZNFX1-AS1 的生物学效应。通过一系列实验评估 lncRNA ZNFX1-AS1 和 miR-144 之间的调节关系。我们发现 lncRNA ZNFX1-AS1 在 CRC 组织和细胞系中表达显著上调,lncRNA ZNFX1-AS1 的表达与 CRC 中侵袭性肿瘤表型和不良预后相关。功能上,lncRNA ZNFX1-AS1 的敲低抑制了细胞增殖、侵袭、体外和体内肿瘤发生和转移。进一步的研究表明,lncRNA ZNFX1-AS1 作为 miR-144 的竞争性内源性 RNA(ceRNA)发挥作用,从而导致其内源性靶基因 Polycomb 组蛋白增强子锌指蛋白 2(EZH2)的下调。我们发现 lncRNA ZNFX1-AS1 在 CRC 中显著上调,新鉴定的 lncRNA ZNFX1-AS1-miR-144-EZH2 轴参与 CRC 进展的调节,可能作为 CRC 患者的潜在治疗靶点。