乳腺癌中miR-222-3p上皮-间质转化相关靶基因的鉴定与综合分析

Identification and comprehensive analysis of epithelial-mesenchymal transition related target genes of miR-222-3p in breast cancer.

作者信息

Fang Yutong, Zhang Qunchen, Chen Chunfa, Chen Zexiao, Zheng Rongji, She Chuanghong, Zhang Rendong, Wu Jundong

机构信息

The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.

The Department of Central Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.

出版信息

Front Oncol. 2023 Jul 20;13:1189635. doi: 10.3389/fonc.2023.1189635. eCollection 2023.

BACKGROUND

Epithelial-mesenchymal transition (EMT) is a crucial mechanism that microRNA-222-3p (miR-222-3p) promotes breast cancer (BC) progression. Our study aimed to identify EMT-associated target genes (ETGs) of miR-222-3p for further analysis of their roles in BC based on bioinformatics tools.

METHODS

Based on bioinformatics analysis, we identified 10 core ETGs of miR-222-3p. Then, we performed a comprehensive analysis of 10 ETGs and miR-222-3p, including pathway enrichment analysis of ETGs, differential expression, clinical significance, correlation with immune cell infiltration, immune checkpoint genes (ICGs) expression, tumor mutational burden (TMB), microsatellite instability (MSI), stemness, drug sensitivity, and genetic alteration.

RESULTS

The expression of miR222-3p in basal-like BC was significantly higher than in other subtypes of BC and the normal adjacent tissue. Pathway analysis suggested that the ETGs might regulate the EMT process via the PI3K-Akt and HIF-1 signaling pathway. Six of the 10 core ETGs of miR-222-3p identified were down-expressed in BC, which were , and , and , and were up-expressed in BC, which also showed potential diagnostic values in BC. Prognosis analysis revealed that higher and expressions were related to a better prognosis, and higher BIRC5 and miR-222-3p expressions were related to a worse prognosis. Most ETGs and miR-222-3p were positively correlated with various infiltration of various immune cells and ICGs expression. Lower TMB scores were correlated with higher expression of and , and higher was related to a higher TMB score. Lower expression of , , and were associated with higher MSI scores. Higher expression of ETGs was associated with lower mRNAsi scores, except and miR-222-3p conversely. Most ETGs and miR-222-3p expression were negatively correlated with the drug IC50 values. The analysis of the genetic alteration of the ETGs suggested that amplification was the main genetic alteration of eight ETGs except for and .

CONCLUSION

MiR-222-3p might be a specific biomarker of basal-like BC. We successfully identify 10 core ETGs of miR-222-3p, some might be useful diagnostic and prognostic biomarkers. The comprehensive analysis of 10 ETGs and miR-222-3p indicated that they might be involved in the development of BC, which might be novel therapeutic targets for the treatment of BC.

背景

上皮-间质转化（EMT）是一种关键机制，微小RNA-222-3p（miR-222-3p）可促进乳腺癌（BC）进展。我们的研究旨在基于生物信息学工具鉴定miR-222-3p的EMT相关靶基因（ETGs），以进一步分析它们在BC中的作用。

方法

基于生物信息学分析，我们鉴定了miR-222-3p的10个核心ETGs。然后，我们对10个ETGs和miR-222-3p进行了全面分析，包括ETGs的通路富集分析、差异表达、临床意义、与免疫细胞浸润的相关性、免疫检查点基因（ICGs）表达、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、干性、药物敏感性和基因改变。

结果

miR222-3p在基底样BC中的表达显著高于其他BC亚型和正常相邻组织。通路分析表明，ETGs可能通过PI3K-Akt和HIF-1信号通路调节EMT过程。鉴定出的miR-222-3p的10个核心ETGs中有6个在BC中低表达，分别是，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，，