Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Clinical Laboratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
J Cell Physiol. 2019 May;234(5):7266-7278. doi: 10.1002/jcp.27484. Epub 2018 Oct 26.
Emerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR-335-5p, isolating miR-335-5p from its target gene Rho-associated coiled-coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR-335-5p. Further cellular behavioral experiments revealed that miR-335-5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR-335-5p, suggesting a novel potential therapeutic target for cervical cancer.
越来越多的证据强调了长非编码 RNA(lncRNA)在许多恶性肿瘤的发生和发展中的关键调控作用。分化拮抗非蛋白编码 RNA(DANCR)是一种新型 lncRNA,广泛参与多种人类癌症的发生发展。然而,DANCR 的功能及其在宫颈癌中的潜在分子机制尚不清楚。在本研究中,我们发现 DANCR 在宫颈癌组织和细胞中显著上调,并与宫颈癌患者的不良预后密切相关。此外,DANCR 的敲低抑制了宫颈癌细胞在体外的增殖、迁移和侵袭,表明 DANCR 在宫颈癌中发挥癌基因的作用。此外,我们验证了 DANCR 可以直接与 miR-335-5p 结合,将 miR-335-5p 从其靶基因 Rho 相关卷曲螺旋蛋白激酶 1(ROCK1)中分离出来。功能分析表明,DANCR 通过竞争性结合 miR-335-5p 来调节 ROCK1 的表达。进一步的细胞行为实验表明,miR-335-5p 模拟物和 ROCK1 敲低通过挽救实验逆转了上调的 DANCR 对宫颈癌细胞增殖、迁移、侵袭和上皮间质转化(EMT)的影响。总之,本研究表明 DANCR 通过作为竞争性内源性 RNA(ceRNA)发挥作用,通过海绵吸附 miR-335-5p 来调节 ROCK1 的表达,从而促进宫颈癌的进展,为宫颈癌提供了一个新的潜在治疗靶点。