Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, 570020, Karnataka, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India.
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, 570020, Karnataka, India.
Comput Biol Med. 2021 Aug;135:104601. doi: 10.1016/j.compbiomed.2021.104601. Epub 2021 Jun 22.
Breast tumors enriched with breast cancer stem cells (BCSCs), play a crucial role in metastasis and tumor relapse. Hence, targeting BCSCs may lead to efficacious breast cancer therapy. BCSCs have a unique expression of stemness markers, including Nanog, POU5F1, SOX2, and CD44, which play a vital role in cancer stem cell properties. However, the regulation of microRNAs (miRNAs)-mediated cancer stem cell marker expressions is largely unclear.
MIENTURNET was used to predict miRNA-target interactions. miR-TV, UALCAN and GEPIA databases were used to analyze the expression of miR-145-5p and SOX2. Survival analysis was obtained by cBioportal, KM plotter and Breast Cancer Gene-Expression Miner. RNAComposer was used to perform miRNA-mRNA duplex prediction. In vitro mRNA and miRNA analysis was performed by qRT-PCR.
It was observed that miR-145-5p was the common miRNA targeting stemness markers. miR-145-5p expression was found to be lower in breast cancer patients compared to healthy subjects. Based on survival analysis, low expression of miR-145-5p and high expression of SOX2 led to a poor overall survival rate in breast cancer patients. Pathway enrichment analysis indicated that SOX2 was highly enriched with transcription factors. Moreover, SOX2 expression level was also upregulated in axillary metastatic lymph nodules. Further, in vitro ectopic expression of miR-145-5p by its mimic downregulated the SOX2 expression compared to the control mimic. Overall, SOX2 was a direct target for miR-145-5p as per the binding and minimal-free energy.
In this study, miR-145-5p targeting SOX2 was identified as a potential predictive biomarker for breast cancer stemness.
富含乳腺癌干细胞（BCSCs）的乳腺肿瘤在转移和肿瘤复发中起着至关重要的作用。因此，针对 BCSCs 可能会导致有效的乳腺癌治疗。BCSCs 具有独特的干性标志物表达，包括 Nanog、POU5F1、SOX2 和 CD44，它们在癌症干细胞特性中起着至关重要的作用。然而，miRNA 介导的癌症干细胞标志物表达的调控在很大程度上尚不清楚。
使用 MIENTURNET 预测 miRNA 靶标相互作用。使用 miR-TV、UALCAN 和 GEPIA 数据库分析 miR-145-5p 和 SOX2 的表达。通过 cBioportal、KM plotter 和 Breast Cancer Gene-Expression Miner 获得生存分析。使用 RNAComposer 进行 miRNA-mRNA 双工预测。通过 qRT-PCR 进行体外 mRNA 和 miRNA 分析。
观察到 miR-145-5p 是靶向干性标志物的常见 miRNA。与健康受试者相比，乳腺癌患者的 miR-145-5p 表达较低。基于生存分析，miR-145-5p 表达低和 SOX2 表达高导致乳腺癌患者总体生存率差。通路富集分析表明 SOX2 高度富集转录因子。此外，SOX2 的表达水平在腋窝转移性淋巴结中也上调。进一步，通过其模拟物的外源性表达 miR-145-5p 可下调与对照模拟物相比的 SOX2 表达。总体而言，根据结合和最小自由能，SOX2 是 miR-145-5p 的直接靶标。
在这项研究中，鉴定出 miR-145-5p 靶向 SOX2 是乳腺癌干性的潜在预测生物标志物。
