Abstract
BackgroundLong non-coding RNAs (lncRNAs) are novel regulatory molecules in breast cancer development. LncRNA LUCAT1 is a potential tumor promoter in human cancers. In this study, we aimed to explore the role of LUCAT1 in human breast cancer tissues and cells.MethodsA total of 31 breast cancer patients who underwent tumor resection, but without chemo- or radiotherapy or acute lung/heart/kidney diseases, provided tumor and adjacent normal tissues. Bioinformatic analysis, qRT-PCR, and luciferase reporter assay were carried out during the study.ResultsqRT-PCR analysis indicated that, compared with the adjacent tissues and MCF-10A normal breast epithelial cells, LUCAT1 was markedly up-regulated in the breast cancer tissues and five BC cell lines, including MDA-MB-231, MDA-MB-468, MDA-MB-435, SKBR3, and MCF-7. The knockdown of LUCAT1, through the transfection of small interfering RNA (siRNA) specific to LUCAT1, resulted in inhibition of proliferation in breast cancer cells. The expression levels of miR-181a-5p were decreased in the breast cancer tissues and five BC cell lines. Bioinformatic analysis and luciferase reporter assay suggested the interaction between miR-181a-5p and LUCAT1. In addition, the effects of LUCAT1 on promoting cell proliferation were attenuated by overexpression of miR-181a-5p through the transfection of miR-181a-5p mimic. Moreover, bioinformatics and luciferase reporter assay confirmed that miR-181a-5p targeted the 3′-UTR region of KLF6 and KLF15 mRNA, which were two tumor suppressor genes. LUCAT1/miR-181a-5p axis regulated the expression of KLF6 and KLF15 both in vitro and in vivo.ConclusionsOur data indicate that LUCAT1/miR-181a-5p axis can serve as a novel therapeutic target in breast cancer.
Highlights
Long non-coding RNAs are novel regulatory molecules in breast cancer development
LUCAT1 is upregulated in breast cancer The expression levels of LUCAT1 in Breast cancer (BC) tissues were compared with that of adjacent tissues, which showed a significant upregulation of LUCAT1 in BC tissues (p < 0.01, Fig. 1a and b)
The results showed a considerable overexpression of LUCAT1 in the BC cell lines compared to that in MCF-10A cells (p < 0.05, Fig. 1c)
Summary
Long non-coding RNAs (lncRNAs) are novel regulatory molecules in breast cancer development. LncRNA LUCAT1 is a potential tumor promoter in human cancers. We aimed to explore the role of LUCAT1 in human breast cancer tissues and cells. While huge improvement of the survival of BC patients with localized cancer has been made, treatment of late-stage cancers, which are metastatic and characterized by chemoresistance, Emerging evidences has indicated that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), which are two classes of non-coding RNAs in human genome, are important regulators of cancers by serving as post-transcriptional regulators that activate or suppress oncogenes to mediate the proliferation, invasion, metastasis and chemoresistance of cancer cells [3, 4]. This study aimed to investigate the role of LUCAT1 in BC
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