Long non-coding RNA LINC0085R promotes cells proliferation, migration and invasion by acting as a ceRNA of miR-22-3p in colorectal cancer

Long non-coding RNA LINC0085R promotes cells proliferation, migration and invasion by acting as a ceRNA of miR-22-3p in colorectal cancer
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DOI:
10.1080/21691401.2018.1544143
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发表时间:
2019-01-01
影响因子:
5.8
通讯作者:
Song, Hang
Song, Hang
中科院分区:
工程技术2区
文献类型:
--
作者:
Sha, Qian-Kun;Chen, Lin;Song, Hang

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虽然长非编码RNA LINC 00858(LINC 00858)已被证明参与其他组织的肿瘤,但其参与结直肠癌(CRC)的情况仍然未知。我们的目的是研究LINC 00858在人CRC中的表达和机制。在本研究中,我们首先通过在线数据和RT-PCR检测发现LINC 00858在结直肠癌组织和细胞系中表达显著上调。临床检测发现LINC 00858高表达与晚期临床进展和不良预后显著相关。多因素分析显示LINC 00858高表达是结直肠癌患者预后不良的独立因素。失功能实验表明,LINC 00858基因的敲除抑制了大肠癌细胞的增殖、迁移和侵袭,并促进了细胞凋亡。生物信息学分析、双荧光素酶报告基因分析和蛋白质印迹分析表明,LINC 00858作为竞争性内源RNA抑制miR-22- 3 p,从而控制其下游靶点YWHAZ。提示LINC 00858可能通过miR-22- 3 p/YWHAZ轴发挥作用。据我们所知,这是第一个报告,显示LINC 00858在CRC的进展中的作用。LINC 00858在结直肠癌的发生发展中起重要作用,可能成为一种新的预后因子和治疗靶点。
Though long non-coding RNA LINC00858 (LINC00858) has been shown to be involved in tumours of other tissues, its involvement in colorectal cancer (CRC) is still unknown. We aimed to investigated expression and mechanism LINC00858 in human CRC. In this study, we firstly found that LINC00858 expression was significantly up-regulated in both CRC tissues and cell lines by both online data and RT-PCR assay. Then, clinical assay revealed that high LINC00858 expression was significantly associated with advanced clinical progression and poor prognosis. Multivariate analysis demonstrated that high LINC00858 expression was an independent poor prognostic factor for CRC patients. Moreover, lost-offunction assay indicated that knockdown of LINC00858 suppressed CRC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistically, bioinformatics analysis, dual-luciferase reporter assays, and western blot assays showed that LINC00858 functioned as competing endogenous RNA to repress miR-22-3p, which controlled its down-stream target YWHAZ. Then, we suggested that LINC00858 exerted its function through the miR-22-3p/YWHAZ axis. To our knowledge, this is the first report which showed the role of LINC00858 in the progression of CRC. Our findings indicated that LINC00858 played an important role in CRC, and may serve as a novel prognostic factor and therapeutic target.