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Abstract
BackgroundEmerging 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.MethodsThe 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.ResultsLINC00511 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.ConclusionIn 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.
Highlights
Breast cancer is one of the most common cancers in women worldwide and is the leading cause of cancer-related death in women [1,2,3]
LncRNA LINC00511 is ectopically over-expressed in the breast cancer tissues and cells compared to normal tissue and cells After comparison and screening, LINC00511 was found to be significantly up-regulated in the breast cancer tissues (Table 1)
As regarding to the role of Long noncoding RNA (lncRNA) on the breast cancer cancer stem cells (CSCs) properties, we discover the vital pathway of LINC00511/miR-185-3p/E2F1/Nanog
Summary
Breast cancer is one of the most common cancers in women worldwide and is the leading cause of cancer-related death in women [1,2,3]. Long noncoding RNAs (lncRNAs) play a role in epigenetic regulation in human pathophysiology [9,10,11] and a large have been found to participate in cancer tumorigenesis [12]. H19 acts as a competitive endogenous RNA for miRNA let-7 resulting in the release of hypoxia-inducible factor 1α (HIF-1α), leading to increased PDK1 expression, thereby regulating the cancer stem-like characteristics [14]. LINC00511 binds histone methyltransferase EZH2 and specifies the histone modification pattern on p57 [15] It acts as an oncogene in squamous cell carcinoma and pancreatic ductal adenocarcinoma [16, 17]. 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. This research puts emphasis on the function of LINC00511 on the breast cancer tumourigenesis and stemness, and investigates the in-depth mechanism
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