Department of General Surgery, Tianjin Union Medical Center, Jieyuan Road 190, Hongqiao District, Tianjin, 300121, China.
NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.
Int J Med Sci. 2020 Jun 27;17(11):1589-1597. doi: 10.7150/ijms.46698. eCollection 2020.
Evidence shows that long noncoding RNAs (lncRNAs) play key roles in various cancers, including colorectal cancer. In this current study, we found that the expression of ZEB1-AS1 in colorectal cancer tissues and cell lines was significantly upregulated, and positively correlated with advanced stage of colorectal cancer. Kaplan-Meier assays also indicated that the expression of ZEB1-AS1 was correlated with poor prognosis in patients with colorectal cancer. Knocking down of ZEB1-AS1 inhibited the proliferation of colorectal cancer cells. Subcellular fractionation analyses suggested that ZEB1-AS1 was majorly distributed in cytoplasm of SW480 and LOVO cells. Thus, ZEB1-AS1 might act as a competing endogenous RNA. MicroRNA array analysis suggested that miR-141-3p was significantly downregulated in CRC tissues, which was further verified by RT-qPCR. The results of luciferase reporter assay proved that miR-141-3p was a target of ZEB1-AS1. Functionally, miR-141-3p inhibitor reversed the anti-proliferation effect of sh-ZEB1-AS1 on colorectal cancer cells. Collectively, ZEB1-AS1 may contribute to colorectal cancer cell proliferation by sponging miR-141-3p.
证据表明,长链非编码 RNA(lncRNAs)在包括结直肠癌在内的多种癌症中发挥着关键作用。在本研究中,我们发现 ZEB1-AS1 在结直肠癌组织和细胞系中的表达明显上调,并与结直肠癌的晚期阶段呈正相关。Kaplan-Meier 分析还表明,ZEB1-AS1 的表达与结直肠癌患者的不良预后相关。敲低 ZEB1-AS1 抑制了结直肠癌细胞的增殖。亚细胞分离分析表明,ZEB1-AS1 主要分布在 SW480 和 LOVO 细胞的细胞质中。因此,ZEB1-AS1 可能作为竞争内源性 RNA 发挥作用。miRNA 芯片分析表明,miR-141-3p 在 CRC 组织中明显下调,进一步通过 RT-qPCR 验证。荧光素酶报告基因实验的结果证实,miR-141-3p 是 ZEB1-AS1 的靶标。功能上,miR-141-3p 抑制剂逆转了 sh-ZEB1-AS1 对结直肠癌细胞增殖的抑制作用。综上所述,ZEB1-AS1 可能通过海绵吸附 miR-141-3p 促进结直肠癌细胞增殖。