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混合组学分析乳腺癌:长链非编码 RNA linc01561 作为 ceRNA 参与乳腺癌的进展。

Mixomics analysis of breast cancer: Long non-coding RNA linc01561 acts as ceRNA involved in the progression of breast cancer.

机构信息

Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.

Department of Opthalmology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.

出版信息

Int J Biochem Cell Biol. 2018 Sep;102:1-9. doi: 10.1016/j.biocel.2018.06.003. Epub 2018 Jun 8.

Abstract

OBJECTIVE

This study aimed at finding the long non-coding RNA (lncRNA), miRNA and mRNA which played critical roles in breast cancer (BrCa) by using mixOmics R package.

METHOD

The BrCa dataset were obtained from TCGA and then analyzed using "DESeq2" R package. Multivariate analyses were performed with the "mixOmics" R package and the first component of the stacked partial least-Squares discriminant analysis results were used for searching the interested lncRNA, miRNA and mRNA. qRT-PCR was applied to identify the bioinformatics results in four BrCa cell lines (MCF7, BT-20, ZR-75-1, and MX-1) and the breast epithelial cell line MCF-10 A. Then cells (MCF-1 and MX-1) were transfected with si-linc01561, miR-145-5p mimics and si-MMP11 to further investigate the effects of linc01561, miR-145-5p and MMP11 on the BrCa cells proliferation and apoptosis.

RESULTS

MixOmics results showed that linc01561, miR-145-5p and MMP11 might play important roles in BrCa. qRT-PCR results identified that in BrCa cell lines, linc01561 and MMP11 were higher expressed while miR-145-5p was lower expressed compared with those in epithelial cell line. The linc01561 inhibition elevated miR-145-5p expression and then suppressed MMP11 expression. Moreover, linc01561 inhibition suppressed the BrCa cells proliferation and promoted the apoptosis, which was realized by up-regulating expression of miR-145-5p and down-regulating expression of MMP11.

CONCLUSION

In summary, the findings of this study, based on ceRNA theory, combining the research foundation of miR-145-5p and MMP11, and taking linc01561 as a new study point, provide new insight into molecular-level reversing proliferation and apoptosis of BrCa.

摘要

目的

本研究旨在通过使用 mixOmics R 包来寻找在乳腺癌(BrCa)中起关键作用的长非编码 RNA(lncRNA)、miRNA 和 mRNA。

方法

从 TCGA 获得 BrCa 数据集,然后使用“DESeq2”R 包进行分析。使用“mixOmics”R 包进行多变量分析,将堆叠偏最小二乘判别分析结果的第一个分量用于搜索感兴趣的 lncRNA、miRNA 和 mRNA。qRT-PCR 用于鉴定四个 BrCa 细胞系(MCF7、BT-20、ZR-75-1 和 MX-1)和乳腺上皮细胞系 MCF-10A 中的生物信息学结果。然后,用 si-linc01561、miR-145-5p 模拟物和 si-MMP11 转染细胞(MCF-1 和 MX-1),进一步研究 linc01561、miR-145-5p 和 MMP11 对 BrCa 细胞增殖和凋亡的影响。

结果

MixOmics 结果表明,linc01561、miR-145-5p 和 MMP11 可能在 BrCa 中起重要作用。qRT-PCR 结果表明,在 BrCa 细胞系中,linc01561 和 MMP11 的表达高于上皮细胞系,而 miR-145-5p 的表达则较低。抑制 linc01561 可上调 miR-145-5p 的表达,进而抑制 MMP11 的表达。此外,抑制 linc01561 可抑制 BrCa 细胞的增殖并促进凋亡,这是通过上调 miR-145-5p 的表达和下调 MMP11 的表达来实现的。

结论

综上所述,本研究基于 ceRNA 理论,结合 miR-145-5p 和 MMP11 的研究基础,以 linc01561 为新的研究点,为分子水平逆转 BrCa 的增殖和凋亡提供了新的见解。

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