一种新型长链非编码 RNA，Lnc-OC1，通过海绵吸附 miR-34a 和 miR-34c 促进卵巢癌细胞增殖和迁移。

A novel lncRNA, Lnc-OC1, promotes ovarian cancer cell proliferation and migration by sponging miR-34a and miR-34c.

机构信息

Department of Immunology and Microbiology, Basic Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China; Department of Biochemistry and Biophysics, Texas A&M University and Texas AgriLife Research, College Station, TX 77843-2128, USA.

出版信息

J Genet Genomics. 2018 Mar 20;45(3):137-145. doi: 10.1016/j.jgg.2018.03.001. Epub 2018 Mar 6.

DOI:10.1016/j.jgg.2018.03.001

PMID:29576507

Abstract

Long non-coding RNAs (lncRNAs) have been reported to be of great importance in tumorigenesis and progression of a variety of cancers. However, the role of lncRNAs in ovarian cancer (OC) remains largely unknown. In the present study, we identified a novel lncRNA, LOC100288181 (named as Lnc-OC1), which acted as a key regulator in the development and progression of OC. The combined Gene Expression Omnibus (GEO) database analysis revealed that Lnc-OC1 was significantly upregulated in OC tissues and Kaplan-Meier survival analysis confirmed that high Lnc-OC1 expression was associated with poor prognosis of OC patients. Importantly, we also demonstrated that knockdown of Lnc-OC1 suppressed cell proliferation, colony formation, invasion and migration in vitro and inhibited tumorigenicity in vivo. Mechanistically, Lnc-OC1 repressed the expression of endogenous miR-34a and miR-34c as a sponge and vice versa. Moreover, rescue experiments demonstrated that the oncogenic function of Lnc-OC1 at least partially depended on suppressing miR-34a and miR-34c. In conclusion, our results suggest that the Lnc-OC1-miR-34a/34c axis may play a pivotal role in OC, and may serve as a potential diagnostic biomarker and a powerful therapeutic target for OC.

摘要

长链非编码 RNA（lncRNAs）在多种癌症的发生和进展中具有重要作用。然而，lncRNAs 在卵巢癌（OC）中的作用在很大程度上尚不清楚。在本研究中，我们鉴定了一种新型 lncRNA，LOC100288181（命名为 Lnc-OC1），它在 OC 的发展和进展中起关键调节作用。联合基因表达综合数据库（GEO）分析显示，Lnc-OC1 在 OC 组织中显著上调，Kaplan-Meier 生存分析证实高表达 Lnc-OC1 与 OC 患者预后不良相关。重要的是，我们还证明了敲低 Lnc-OC1 可抑制体外细胞增殖、集落形成、侵袭和迁移，并抑制体内肿瘤发生。机制上，Lnc-OC1 作为海绵抑制内源性 miR-34a 和 miR-34c 的表达，反之亦然。此外，挽救实验表明 Lnc-OC1 的致癌功能至少部分依赖于抑制 miR-34a 和 miR-34c。总之，我们的结果表明 Lnc-OC1-miR-34a/34c 轴可能在 OC 中发挥关键作用，并可能作为 OC 的潜在诊断生物标志物和强大的治疗靶点。