Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Basic Medical Sciences Department, College of Medicine, Dar Al Uloom University, Riyadh 7222, Saudi Arabia.
Int J Mol Sci. 2020 Nov 14;21(22):8589. doi: 10.3390/ijms21228589.
miRNAs, a group of short noncoding RNAs, are key regulators of fundamental cellular processes and signaling pathways. Dysregulation of miRNA expression with known oncogenic or tumor suppressor functions has been associated with neoplastic transformation. Numerous studies have reported dysregulation of miRNA-141, miR-181b1, and miR-23b in a wide range of malignancies, including breast cancer. To the best of our knowledge, no previous study had demonstrated the expression of miR-141-3p, miR-181b1-5p, and miR-23b-3p in different histological grades and molecular subtypes of breast cancer. Here, we identified differential expression of these three miRNAs in breast cancer tissues compared with benign breast fibroadenomas. In addition, high expression levels of miR-141-3p and miR-181b1-5p are strongly associated with aggressive breast carcinomas. We also confirmed the clinical potential of using the three miRNAs individually or combined as diagnostic and prognostic markers in breast cancer. Using bioinformatics analyses, we identified 23 hub genes of these three miRNAs which are involved in key signaling pathways in breast cancer. Furthermore, the KM plotter online database analysis demonstrates the association between elevated expression of miR-141 and miR-181b and shorter overall survival of breast cancer patients. Together, our data suggest an oncogenic role of the studied miRNAs and highlight their molecular roles and potential clinical applications in breast cancer.
miRNAs 是一组短的非编码 RNA,是基本细胞过程和信号通路的关键调节因子。miRNA 表达的失调与已知的致癌或肿瘤抑制功能有关,与肿瘤转化有关。许多研究报告了 miRNA-141、miR-181b1 和 miR-23b 在广泛的恶性肿瘤中的失调,包括乳腺癌。据我们所知,以前没有研究表明 miR-141-3p、miR-181b1-5p 和 miR-23b-3p 在乳腺癌的不同组织学分级和分子亚型中表达。在这里,我们发现这三种 miRNA 在乳腺癌组织中的表达与良性乳腺纤维腺瘤不同。此外,miR-141-3p 和 miR-181b1-5p 的高表达水平与侵袭性乳腺癌强烈相关。我们还证实了单独使用这三种 miRNA 或联合使用作为乳腺癌诊断和预后标志物的临床潜力。通过生物信息学分析,我们鉴定出这三种 miRNA 的 23 个枢纽基因,它们参与了乳腺癌中的关键信号通路。此外,KM plotter 在线数据库分析表明,miR-141 和 miR-181b 的表达升高与乳腺癌患者总生存期缩短有关。总之,我们的数据表明研究的 miRNA 具有致癌作用,并强调了它们在乳腺癌中的分子作用和潜在的临床应用。