Mahmoud Marwa M, Sanad Eman F, Elshimy Reham A A, Hamdy Nadia M
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Clinical and Chemical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Front Oncol. 2021 Oct 20;11:749753. doi: 10.3389/fonc.2021.749753. eCollection 2021.
Breast cancer (BC) is the leading cause of female cancer-related mortalities. Evidence has illustrated the role of long non-coding RNAs (lncRNA) and microRNAs (miRNA) as promising pool of protein non-coding regulators, for tuning the aggressiveness of several malignancies. This research aims to unravel the expression pattern and the emphases of the diagnostic value of the long intergenic ncRNA00511 (LINC00511) and its downstream microRNA (miR-185-3p) and the pathogenic significance of the onco-miR-301a-3p in naïve BC patients. LINC00511 was chosen and validated, and its molecular binding was confirmed using bioinformatics. LINC00511 was measured in 25 controls and 70 patients using qPCR. The association between the investigated ncRNA's expression and the BC patients' clinicopathological features was assessed. Receiver operating characteristic (ROC) curve was blotted to weigh out their diagnostic efficacy over the classical tumor markers (TMs). Bioinformatics and Spearman correlation were used to predict the interaction between LINC00511, miR-185-3p, and miR-301a-3p altogether to patients' features. LINC00511 and miR-301a-3p, in BC patients' blood, were overexpressed, and their median levels increased significantly, while miR-185-3p was, in contrast, downregulated, being decreased fourfold. LINC00511 was elevated in BC early stages, when compared to late stages ( < 0.0003). LINC00511, miR-185-3p, and miR-301a-3p showed AUC superior to classical TMs, allowing us to conclude that the investigated ncRNAs, in BC patients' liquid biopsy, are novel diagnostic molecular biomarker signatures. Lymph node metastasis (LNM) and advanced tumor grade were directly correlated with LINC00511 significantly. Additionally, both LINC00511 and miR-301a-3p were positively correlated with the aggressiveness of BC, as manifested in patients with larger tumors (>2 cm) at ( < 0.001). Therefore, these findings aid our understanding of BC pathogenesis, in the clinical setting, being related in part to the LINC00511/miR axis, which could be a future potential therapeutic target.
乳腺癌(BC)是女性癌症相关死亡的主要原因。有证据表明,长链非编码RNA(lncRNA)和微小RNA(miRNA)作为有前景的蛋白质非编码调节因子库,在调节多种恶性肿瘤的侵袭性方面发挥着作用。本研究旨在揭示长链基因间非编码RNA00511(LINC00511)及其下游微小RNA(miR-185-3p)的表达模式和诊断价值重点,以及致癌微小RNA-301a-3p在初治BC患者中的致病意义。选择并验证了LINC00511,并使用生物信息学证实了其分子结合。使用qPCR在25名对照和70名患者中检测了LINC00511。评估了所研究的ncRNA表达与BC患者临床病理特征之间的关联。绘制了受试者工作特征(ROC)曲线,以衡量它们相对于经典肿瘤标志物(TMs)的诊断效能。使用生物信息学和Spearman相关性来预测LINC00511、miR-185-3p和miR-301a-3p之间与患者特征的相互作用。在BC患者血液中,LINC00511和miR-301a-3p过表达,其中位数水平显著升高,而miR-185-3p则相反,下调了四倍。与晚期相比,LINC00511在BC早期升高(<0.0003)。LINC00511、miR-185-3p和miR-301a-3p的AUC优于经典TMs,这使我们得出结论,在BC患者的液体活检中,所研究的ncRNAs是新型诊断分子生物标志物特征。淋巴结转移(LNM)和高级别肿瘤分级与LINC00511显著直接相关。此外,LINC00511和miR-301a-3p均与BC的侵袭性呈正相关,如在肿瘤较大(>2 cm)的患者中所示(<0.001)。因此,这些发现有助于我们在临床环境中理解BC的发病机制,部分与LINC00511/miR轴相关,这可能是未来潜在的治疗靶点。