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长链非编码 RNA opa 相互作用蛋白 5 反义转录本 1 通过海绵吸附 miR-143-3p 上调整合素 α6 表达促进宫颈癌增殖和侵袭。

Long noncoding RNA opa-interacting protein 5 antisense transcript 1 promotes proliferation and invasion through elevating integrin α6 expression by sponging miR-143-3p in cervical cancer.

机构信息

Department of Gynecology Oncology, Xinxiang Central Hospital, XinXiang, China.

出版信息

J Cell Biochem. 2019 Jan;120(1):907-916. doi: 10.1002/jcb.27454. Epub 2018 Sep 6.

Abstract

An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in cervical cancer (CC) progression. However, the roles and underlying mechanisms of lncRNA opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) involved in the CC remain unclear. In the current study, we found that lncRNA OIP5-AS1 was upregulated in CC tissues and cell lines. High OIP5-AS1 expression was significantly correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and poor overall survival of patients with CC. Using in vitro function assays, we showed that OIP5-AS1 suppression significantly decreased the proliferation, colony formation, and invasion ability of CC cells. Moreover, we revealed that OIP5-AS1 could act as a competing endogenous RNA of miR-143-3p to regulate the ITGA6 expression. Rescue assays showed that miR-143-3p inhibitors or ITGA6 overexpression could reverse the inhibitory effects of OIP5-AS1 suppression on the proliferation and invasion in CC cells. In addition, OIP5-AS1 suppression reduced tumor growth in vivo. In conclusion, we demonstrated that OIP5-AS1 promoted proliferation and invasion of CC cells via increasing the ITGA6 expression by sponging miR-143-3p, which might be an effective therapeutic target for the treatment of patients with CC.

摘要

越来越多的研究表明,长链非编码 RNA(lncRNA)在宫颈癌(CC)进展中发挥重要作用。然而,lncRNA opa 相互作用蛋白 5 反义转录本 1(OIP5-AS1)在 CC 中所涉及的作用和潜在机制仍不清楚。在本研究中,我们发现 lncRNA OIP5-AS1 在 CC 组织和细胞系中上调。高 OIP5-AS1 表达与国际妇产科联盟(FIGO)晚期、淋巴结转移和 CC 患者总体生存率差显著相关。通过体外功能测定,我们表明 OIP5-AS1 抑制显著降低了 CC 细胞的增殖、集落形成和侵袭能力。此外,我们揭示了 OIP5-AS1 可以作为 miR-143-3p 的竞争性内源性 RNA 来调节 ITGA6 的表达。挽救实验表明,miR-143-3p 抑制剂或 ITGA6 过表达可以逆转 OIP5-AS1 抑制对 CC 细胞增殖和侵袭的抑制作用。此外,OIP5-AS1 抑制减少了体内肿瘤生长。总之,我们证明了 OIP5-AS1 通过海绵吸附 miR-143-3p 增加 ITGA6 的表达来促进 CC 细胞的增殖和侵袭,这可能是治疗 CC 患者的有效治疗靶点。

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