Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis.
Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis.
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DOI：
10.1186/s13046-018-0945-6
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发表时间：
2018-11-27
期刊：
影响因子：
--
通讯作者：
Wei Z
中科院分区：
文献类型：
--
作者：
Lu G;Li Y;Ma Y;Lu J;Chen Y;Jiang Q;Qin Q;Zhao L;Huang Q;Luo Z;Huang S;Wei Z
新的证据表明长链非编码RNA（lncRNA）基因间非蛋白质编码RNA 00511（LINC 00511）在人类肿瘤的发生发展中起着重要作用。然而，LINC 00511在乳腺癌肿瘤发生中的作用仍然未知。本研究着重探讨LINC 00511在乳腺癌发生、发展中的作用，并探讨其深入机制。用RT-PCR检测lncRNA和RNA的表达。使用蛋白质印迹分析测量蛋白质水平。CCK-8法、集落形成实验和transwell实验检测细胞增殖能力和侵袭能力。还对干度进行了球体形成测定。进行生物信息学分析、染色质免疫沉淀（ChIP）和荧光素酶报告基因测定以确认分子结合。LINC 00511在乳腺癌组织中高表达，且高表达与预后不良相关。在功能上，获得和丧失功能的实验显示LINC 00511促进乳腺癌细胞的增殖、球形成能力、干因子（Oct 4、Nanog、SOX 2）表达和肿瘤生长。在机械上，LINC 00511作为miR-185- 3 p的竞争性内源RNA（ceRNA）发挥作用，以积极回收E2 F1蛋白。此外，转录因子E2 F1与Nanog基因的启动子区结合，以促进其转录。综上所述，我们的数据得出结论，LINC 00511/miR-185- 3 p/E2 F1/Nanog轴促进乳腺癌的干性和肿瘤发生，为它们提供了重要的见解。本文的在线版本（10.1186/s13046-018-0945-6）包含补充材料，可供授权用户使用。
Emerging evidence have illustrated the vital role of long noncoding RNAs (lncRNAs) long intergenic non-protein coding RNA 00511 (LINC00511) on the human cancer progression and tumorigenesis. However, the role of LINC00511 in breast cancer tumourigenesis is still unknown. This research puts emphasis on the function of LINC00511 on the breast cancer tumourigenesis and stemness, and investigates the in-depth mechanism. The lncRNA and RNA expression were measured using RT-PCR. Protein levels were measured using western blotting analysis. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Sphere-formation assay was also performed for the stemness. Bioinformatic analysis, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried to confirm the molecular binding. LINC00511 was measured to be highly expressed in the breast cancer specimens and the high-expression was correlated with the poor prognosis. Functionally, the gain and loss-of-functional experiments revealed that LINC00511 promoted the proliferation, sphere-formation ability, stem factors (Oct4, Nanog, SOX2) expression and tumor growth in breast cancer cells. Mechanically, LINC00511 functioned as competing endogenous RNA (ceRNA) for miR-185-3p to positively recover E2F1 protein. Furthermore, transcription factor E2F1 bind with the promoter region of Nanog gene to promote it transcription. In conclusion, our data concludes that LINC00511/miR-185-3p/E2F1/Nanog axis facilitates the breast cancer stemness and tumorigenesis, providing a vital insight for them. The online version of this article (10.1186/s13046-018-0945-6) contains supplementary material, which is available to authorized users.
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