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Long non-coding RNA LINC00511/miR-150/MMP13 axis promotes breast cancer proliferation, migration and invasion
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2020-10-05 , DOI: 10.1016/j.bbadis.2020.165957
GuangHui Shi 1 , YiFei Cheng 2 , Yang Zhang 1 , Rui Guo 3 , Shenglei Li 4 , Xin Hong 1
Affiliation  

Breast cancer is the most common cancer affecting women and one of the leading causes of cancer-related deaths worldwide. In existing studies, some long non-coding RNAs (lncRNAs) are considered to have important regulatory roles in the development of cancers. However, the pathogenic significance of LINC00511 in breast cancer is unclear. In this study, LINC00511 was significantly up-regulated in breast cancer, and its expression level was correlated to poor prognosis of patients with breast cancer. To further study the role of LINC00511 in breast cancer, we knocked down the expression of LINC00511 using siRNAs. Cells transfected with siRNA-2 proliferated, and its metastasis was suppressed. RNA-seq analysis revealed 182 potential targets for LINC00511. The in-silico analysis revealed that differently expressed genes were closely related to signaling mediated by p38-alpha and p38-beta. Subcellular localization showed that LINC00511 was mainly located in the cytoplasm, and knocking down the LINC00511 gene could down-regulate the expression of MMP13. Using bioinformatics analysis combined with dual-luciferase report assay, we finally determined that miR-150 was the direct target of LINC00511. The dual-luciferase report assays also showed that MMP13 was the target of miR-150. LINC00511 knockdown significantly reduced MMP13 protein levels, and miR-150 gene knockdown significantly rescued the down-regulation of MMP13 caused by LINC00511 gene silencing. Moreover, silencing MMP13 and overexpression of miR-150 could reduce the proliferation of breast cancer cells. In conclusion, our data show that LINC00511 is a breast cancer promoter, and the LINC00511/miR-150/MMP13 axis may be a new therapeutic strategy for breast cancer patients.



中文翻译:

长的非编码RNA LINC00511 / miR-150 / MMP13轴可促进乳腺癌的增殖,迁移和侵袭

乳腺癌是影响女性的最常见癌症,也是全球范围内与癌症相关的死亡的主要原因之一。在现有研究中,一些长的非编码RNA(lncRNA)被认为在癌症的发展中具有重要的调节作用。但是,LINC00511在乳腺癌中的致病意义尚不清楚。在这项研究中,LINC00511在乳腺癌中显着上调,其表达水平与乳腺癌患者的不良预后相关。为了进一步研究LINC00511在乳腺癌中的作用,我们使用siRNA敲低了LINC00511的表达。siRNA-2转染的细胞增殖,其转移受到抑制。RNA-seq分析揭示了LINC00511的182个潜在靶标。电脑分析表明,不同表达的基因与p38-alpha和p38-beta介导的信号密切相关。亚细胞定位表明LINC00511主要位于细胞质中,敲除LINC00511基因可能下调MMP13的表达。使用生物信息学分析结合双荧光素酶报告测定法,我们最终确定miR-150是LINC00511的直接靶标。双重荧光素酶报告分析还显示,MMP13是miR-150的靶标。LINC00511敲低可显着降低MMP13蛋白水平,而miR-150基因敲低可显着挽救LINC00511基因沉默引起的MMP13下调。此外,沉默MMP13和miR-150的过度表达可以减少乳腺癌细胞的增殖。结论,

更新日期:2020-10-05
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