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