Department of Mammary and Thyroid Gland Surgery, Youjiang Medical College Affiliated Hospital, Baise, 533000, Guangxi, China.
The First Affiliated Hospital of Jinan university, Huangpu Road, No. 613, Guangzhou, 510630, Guangdong, China.
J Exp Clin Cancer Res. 2018 Nov 27;37(1):289. doi: 10.1186/s13046-018-0945-6.
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.
越来越多的证据表明，长非编码 RNA（lncRNA）长基因间非蛋白编码 RNA 00511（LINC00511）在人类癌症进展和肿瘤发生中起着至关重要的作用。然而，LINC00511 在乳腺癌肿瘤发生中的作用尚不清楚。本研究重点探讨了 LINC00511 在乳腺癌肿瘤发生和干性中的作用，并深入研究了其机制。
使用 RT-PCR 测量 lncRNA 和 RNA 的表达。使用 Western blot 分析测量蛋白质水平。通过 CCK-8、集落形成实验和 Transwell 实验评估细胞增殖能力和侵袭能力。球形成实验也用于评估干性。通过生物信息学分析、染色质免疫沉淀（ChIP）和荧光素酶报告基因实验证实分子结合。
LINC00511 在乳腺癌标本中表达水平较高，高表达与预后不良相关。功能上，获得和丧失功能实验表明，LINC00511 促进了乳腺癌细胞的增殖、球形成能力、干性因子（Oct4、Nanog、SOX2）表达和肿瘤生长。机制上，LINC00511 作为 miR-185-3p 的竞争性内源 RNA（ceRNA），正向恢复 E2F1 蛋白。此外，转录因子 E2F1 与 Nanog 基因启动子区域结合，促进其转录。
总之，我们的数据表明，LINC00511/miR-185-3p/E2F1/Nanog 轴促进了乳腺癌的干性和肿瘤发生，为其提供了重要的见解。
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