Cai Chang, Huo Qiang, Wang Xiaolong, Chen Bing, Yang Qifeng
Department of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, China.
Department of Orthopaedic Surgery, Zibo Central Hospital Affiliated to Shandong University, Zibo, China.
Biochem Biophys Res Commun. 2017 Apr 1;485(2):272-278. doi: 10.1016/j.bbrc.2017.02.094. Epub 2017 Feb 21.
Long noncoding RNAs (lncRNAs) have been proved to play important roles in cellular processes of cancer, including the development, proliferation, and migration of cancer cells. In the present study, we demonstrated small nucleolar RNA host gene 16 (SNHG16) as an oncogene on cell migration in breast cancer. Expression levels of SNHG16 were found to be frequently higher in breast cancer tissues than in the paired noncancerous tissues. Gain- and loss-of-function studies proved that SNHG16 significantly promoted breast cancer cell migration. We predicted SNHG16 as a competitive endogenous RNA (ceRNA) of E2F transcription factor 5 protein (E2F5) via competition for the shared miR-98 through bioinformatics analysis, and proved this regulation using relative quantitative real-time PCR (qRT-PCR), western blot, RNA immunoprecipitation (RIP) assay and luciferase reporter assay. In addition, we identified a positive correlation between SNHG16 and E2F5 in breast cancer tissues. Furthermore, we demonstrated that forced expression of miR-98 could partially abrogate SNHG16-mediated increase of breast cancer cells migration, suggesting that SNHG16 promoted cell migration in a miR-98 dependent manner. Taken together, our findings indicated that SNHG16 induces breast cancer cell migration by competitively binding miR-98 with E2F5, and SNHG16 can serve as a potential therapeutic target for breast cancer treatment.
长链非编码RNA（lncRNAs）已被证明在癌症的细胞过程中发挥重要作用，包括癌细胞的发育、增殖和迁移。在本研究中，我们证明了小核仁RNA宿主基因16（SNHG16）在乳腺癌细胞迁移中作为一种癌基因。发现SNHG16在乳腺癌组织中的表达水平通常高于配对的非癌组织。功能获得和功能丧失研究证明，SNHG16显著促进乳腺癌细胞迁移。通过生物信息学分析，我们预测SNHG16是E2F转录因子5蛋白（E2F5）的竞争性内源RNA（ceRNA），通过竞争共享的miR-98来实现，并使用相对定量实时PCR（qRT-PCR）、蛋白质免疫印迹、RNA免疫沉淀（RIP）试验和荧光素酶报告基因试验证明了这种调控。此外，我们在乳腺癌组织中发现SNHG16与E2F5之间存在正相关。此外，我们证明了miR-98的强制表达可以部分消除SNHG16介导的乳腺癌细胞迁移增加，这表明SNHG16以miR-98依赖的方式促进细胞迁移。综上所述，我们的研究结果表明，SNHG16通过与E2F5竞争性结合miR-98诱导乳腺癌细胞迁移，并且SNHG16可以作为乳腺癌治疗的潜在治疗靶点。
