a Department of Gastroenterology , Huaihe Hospital of Henan University , Kaifeng , Henan China.
Cell Cycle. 2018;17(2):154-161. doi: 10.1080/15384101.2017.1407895. Epub 2018 Jan 17.
The incidence and mortality rate of colorectal cancer (CRC) have been significantly increasing. However, mechanisms involved in CRC progression are still unclear. LncRNA ZFAS1 has been verified as oncogenic molecular in a series of tumors, including CRC. However, the underlying mechanism of ZFAS1 in CRC carcinogenesis remains unclear. In the present study, our data showed that ZFAS1 expression was significantly upregulated in CRC tissues and cell lines. Correlation analysis showed that high ZFAS1 expression was significantly associated with Helicobacter pylori infection, lymph nodes metastasis, advanced TNM stage and poor overall survival of CRC patients. Loss-of-function experiments revealed that ZFAS1 inhibition could markedly suppress CRC cells proliferation and invasion both in vitro and in vivo. Bioinformatics analysis and luciferase reporter assay revealed that ZFAS1 directly interacted with miR-484. Rescue experiments showed that miR-484 inhibitor reversed the tumor suppressing roles of ZFAS1 knockdown on CRC cells. Therefore, our study suggested that ZFAS1 could act as an oncogene in CRC tumorigenesis, and discovered the functional regulatory pathway of ZFAS1 sponging miR-484.
结直肠癌(CRC)的发病率和死亡率一直在显著上升。然而,CRC 进展涉及的机制仍不清楚。LncRNA ZFAS1 已被证实为一系列肿瘤中的致癌分子,包括 CRC。然而,ZFAS1 在 CRC 癌变中的潜在机制尚不清楚。在本研究中,我们的数据表明 ZFAS1 表达在 CRC 组织和细胞系中显著上调。相关性分析表明,ZFAS1 高表达与幽门螺杆菌感染、淋巴结转移、晚期 TNM 分期和 CRC 患者的总体生存不良显著相关。功能丧失实验表明,ZFAS1 抑制可显著抑制 CRC 细胞在体外和体内的增殖和侵袭。生物信息学分析和荧光素酶报告基因实验表明,ZFAS1 可直接与 miR-484 相互作用。挽救实验表明,miR-484 抑制剂逆转了 ZFAS1 敲低对 CRC 细胞的肿瘤抑制作用。因此,我们的研究表明 ZFAS1 可作为 CRC 肿瘤发生中的癌基因,并发现了 ZFAS1 海绵 miR-484 的功能调节途径。