Mohamed Sameh H, Kamal Mohamed M, Reda Ahmed M, Mesbah Noha M, Abo-Elmatty Dina M, Abdel-Hamed Asmaa R
Biochemistry Department, Faculty of Pharmacy, The Egyptian Russian University, Cairo, Egypt.
Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, El Sherouk City, Suez Desert Road, P.O. Box 43, Cairo, 11837, Egypt.
Mol Cell Biochem. 2025 Apr;480(4):2117-2129. doi: 10.1007/s11010-024-05136-4. Epub 2024 Oct 26.
Breast cancer is the most prevalent type of cancer among women worldwide. Non-coding RNAs play a fundamental role in regulating the expression of different genes. MicroRNAs (miRNAs) are known to bind to mRNA and either induce its degradation or repress its translation. Also, miRNA can modulate the expression of long non-coding RNAs (lncRNA) through different mechanisms. This study aims to determine the role of miRNA-205-5p in breast cancer cell lines. miR-205-5p was bioinformatically predicted to interact with LRP6 mRNA and lncRNAs MALAT1, NEAT1, SNHG5, and SNHG16. Then, the levels of miR-205-5p and its target genes and lncRNAs in breast cancer cell lines MCF-7 and MDA-MB-231 were determined. In addition, MCF-7 and MDA-MB-231 breast cancer cells were transfected with miR-205-5p mimic or miRNA mimic negative control using lipofectamine 3000, and the effect of miR-205-5p overexpression on cellular proliferation and migration was assessed. Moreover, we probed the impact of miR-205-5p overexpression on the expression levels of LRP6, Wnt/β-catenin pathway genes, lncRNAs, and apoptotic markers. miR-205-5p upregulation resulted in decreasing the growth and migration and induced apoptosis markers in the two tested breast cancer subtypes. Additionally, miR-205-5p overexpression resulted in decreasing the expression of LRP6 in MCF-7 and MDA-MB-231 cells leading to downregulation of Wnt/β-catenin target genes, c-Myc, cyclin D1, and PPARδ and had various regulatory effects on the expression of lncRNAs MALAT1, NEAT1, SNHG5, and SNHG16. miR-205-5p inhibits the proliferation and migration of breast cancer through diverse mechanisms including targeting LRP6, Wnt/β-catenin pathway, and its regulatory effects on lncRNAs.
乳腺癌是全球女性中最常见的癌症类型。非编码RNA在调节不同基因的表达中起着重要作用。已知微小RNA(miRNA)与信使核糖核酸(mRNA)结合,要么诱导其降解,要么抑制其翻译。此外,miRNA可通过不同机制调节长链非编码RNA(lncRNA)的表达。本研究旨在确定miRNA-205-5p在乳腺癌细胞系中的作用。通过生物信息学预测,miR-205-5p可与低密度脂蛋白受体相关蛋白6(LRP6)mRNA以及lncRNA转移相关肺腺癌转录本1(MALAT1)、核富集转录本1(NEAT1)、小核仁RNA宿主基因5(SNHG5)和小核仁RNA宿主基因16(SNHG16)相互作用。然后,测定了乳腺癌细胞系MCF-7和MDA-MB-231中miR-205-5p及其靶基因和lncRNA的水平。此外,使用脂质体3000将miR-205-5p模拟物或miRNA模拟物阴性对照转染到MCF-7和MDA-MB-231乳腺癌细胞中,并评估miR-205-5p过表达对细胞增殖和迁移的影响。此外,我们探究了miR-205-5p过表达对LRP6、Wnt/β-连环蛋白信号通路基因、lncRNA和凋亡标志物表达水平的影响。miR-205-5p上调导致两种受试乳腺癌亚型的生长和迁移减少,并诱导凋亡标志物。此外,miR-205-5p过表达导致MCF-7和MDA-MB-231细胞中LRP6表达降低,导致Wnt/β-连环蛋白靶基因c-Myc、细胞周期蛋白D1和过氧化物酶体增殖物激活受体δ(PPARδ)下调,并对lncRNA MALAT1、NEAT1、SNHG5和SNHG16的表达产生多种调节作用。miR-205-5p通过多种机制抑制乳腺癌的增殖和迁移,包括靶向LRP6、Wnt/β-连环蛋白信号通路及其对lncRNA的调节作用。