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LncRNA LUCAT1/miR-181a-5p axis promotes proliferation and invasion of breast cancer via targeting KLF6 and KLF15
BMC Molecular and Cell Biology ( IF 2.8 ) Pub Date : 2020-09-30 , DOI: 10.1186/s12860-020-00310-0
Yun Liu , Teng Cheng , Yaying Du , Xiaopeng Hu , Wenfei Xia

Long 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. A 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. qRT-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. Our data indicate that LUCAT1/miR-181a-5p axis can serve as a novel therapeutic target in breast cancer.

中文翻译:

LncRNA LUCAT1 / miR-181a-5p轴通过靶向KLF6和KLF15促进乳腺癌的增殖和侵袭

长非编码RNA(lncRNA)是乳腺癌发展中的新型调控分子。LncRNA LUCAT1是人类癌症中潜在的肿瘤启动子。在这项研究中,我们旨在探讨LUCAT1在人类乳腺癌组织和细胞中的作用。共有31例接受了肿瘤切除但没有化学或放射疗法或急性肺/心脏/肾脏疾病的乳腺癌患者提供了肿瘤和邻近的正常组织。在研究过程中进行了生物信息学分析,qRT-PCR和荧​​光素酶报告基因分析。qRT-PCR分析表明,与邻近组织和MCF-10A正常乳腺上皮细胞相比,LUCAT1在乳腺癌组织和包括MDA-MB-231,MDA-MB-468在内的5种BC细胞系中明显上调,MDA-MB-435,SKBR3和MCF-7。LUCAT1的组合 通过转染针对LUCAT1的小干扰RNA(siRNA),可抑制乳腺癌细胞的增殖。在乳腺癌组织和五个BC细胞系中,miR-181a-5p的表达水平降低。生物信息学分析和荧光素酶报告基因分析表明miR-181a-5p与LUCAT1之间存在相互作用。另外,通过miR-181a-5p模拟物的转染,miR-181a-5p的过表达减弱了LUCAT1促进细胞增殖的作用。此外,生物信息学和荧光素酶报告基因测定证实,miR-181a-5p靶向两个抑癌基因KLF6和KLF15 mRNA的3'-UTR区。LUCAT1 / miR-181a-5p轴在体外和体内均调节KLF6和KLF15的表达。
更新日期:2020-09-30
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