Abstract
BackgroundThe mechanism underlying breast cancer stem cell (BCSCs) characteristics remains to be fully elucidated. Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a pivotal role in regulating BCSCs stemness.MethodsLncRNA LUCAT1 expression was assessed in breast cancer tissues (n = 151 cases) by in situ hybridization. Sphere-formation assay and colony formation assay were used to detect cell self-renewal and proliferation, respectively. RNA immunoprecipitation, RNA pull down and luciferase reporter assays were used to identify LUCAT1 and TCF7L2 as the direct target of miR-5582-3p. The activity of the Wnt/β-catenin pathway was analyzed by TOP/FOP-Flash reporter assays, western blot and immunohistochemistry (IHC).ResultsThis study found LUCAT1 expression was related to tumor size (p = 0.015), lymph node metastasis (p = 0.002) and TNM staging (p < 0.001). High LUCAT1 expression indicated a shorter overall survival (p = 0.006) and disease-free survival (p = 0.011). Furthermore, LUCAT1 was more expressed in BCSCs than in breast cancer cells (BCCs) by lncRNA microarray chips. LUCAT1 up-regulation promoted proliferation of BCCs, while LUCAT1 down-regulation inhibited self-renewal of BCSCs. MiR-5582-3p was directly bound to LUCAT1 and TCF7L2 and negatively regulated their expression. LUCAT1 affected Wnt/β-catenin pathway.ConclusionsLUCAT1 might be a significant biomarker to evaluate prognosis in breast cancer. LUCAT1 increased stem-like properties of BCCs and stemness of BCSCs by competitively binding miR-5582-3p with TCF7L2 and enhancing the Wnt/β-catenin pathway. The LUCAT1/miR-5582-3p/TCF7L2 axis provides insights for regulatory mechanism of stemness, and new strategies for clinical practice.
Highlights
The mechanism underlying breast cancer stem cell (BCSCs) characteristics remains to be fully elucidated
Lung cancer associated transcript 1 (LUCAT1) is over-expressed in the Breast cancer stem cells (BCSCs) than breast cancer cells (BCCs) and related to breast cancer stemness Since the induction and culture of BCSCs was matured in our research group [23], the present study briefly verified the results
We detected LUCAT1 expression in 26 pairs of fresh specimens by quantitative real-time polymerase chain reaction (qRT-PCR) and found LUCAT1 expression in cancer tissues was higher than matched adjacent normal tissues (p < 0.01, Additional file 5: Figure S2a)
Summary
The mechanism underlying breast cancer stem cell (BCSCs) characteristics remains to be fully elucidated. Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a pivotal role in regulating BCSCs stemness. As ‘de-escalation’ requires more valuable evidence and Heterogeneous clusters of tumor cells exist in solid tumors, a special subgroup of which is called cancer stem cells (CSCs), characterized by self-renewal and pluripotency [4, 5]. Breast cancer stem cells (BCSCs) are regarded as the source of tumor development, differentiation, invasion and metastasis, drug resistance and recurrence in breast cancer [6,7,8]. Stem cells has shown attractive prospects in therapy. Studies on stemness regulation of BCSCs are significant in theory and clinical practice
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