BACKGROUND ATP-Binding Cassette subfamily G member 2 (ABCG2) is a semi-transport protein that plays a key role in human diseases, including bladder cancer and lung cancer, and may be resistant to chemotherapy drugs. OBJECTIVE The present study aimed to determine the role and underlying mechanisms of breast cancer resistance protein (ABCG2) in breast cancer. To study the reversal effect of inhibiting ABCG2 expression on the drug resistance of breast cancer cells, and provide new ideas for gene targeted therapy of breast cancer. METHODS The structure and genomic alterations of ABCG2 were systematically investigated using GeneCards and cBioPortal to reveal the genetic alterations (including amplification and deep deletions) of ABCG2. We performed the correlation between ABCG2 expression and clinicopathological parameters using the data in bc-GenExMiner 4.4. Then, the protein-protein interaction and functional enrichment analysis of ABCG2 were performed based on the STRING, bc-GenExMiner 4.4, and Enrichr databases. Besides, we analyzed the pathway activity of genes that interact with ABCG2 using GSCALite and PharmGKB. Using magnetic nanoparticles polyMAG as the carrier of ABCG2-siRNA, polyMAG-ABCG2-siRNA was transfected into the Doxorubicin (DOX)-resistant breast cancer cell line MCF-7/ADR and directly into the tumors in nude mice. Patent US20150328485 points out that magnetic nanoparticles can be attached to an anti-cancer drug, such as an antibody-based anti-cancer drug. RESULTS We found statistically significant correlation between ABCG2 expression and clinicopathological parameters, such as Estrogen Receptor (ER), Progesterone Receptor (PR), and human epidermal growth factor receptor-2 (HER2), and nodal status in breast cancer patients. ABCG2 is closely related to SLC2A9, KIT, ABCG1, and MRPS7, which suggests that these proteins may be functional partners of breast cancer. The expression of ABCG2 is correlated with the activation or inhibition of multiple oncogenic pathways. Moreover, we found that ABCG2 is involved in the DOX signaling pathway. The small interfering RNA (siRNA) carried by magnetic nanoparticles can reduce the expression of ABCG2, thereby significantly improving the therapeutic effect of DOX on tumors. CONCLUSION Our findings provide a more in-depth understanding of ABCG2 as a biomarker for predicting DOX-resistance and insights into the development of related therapeutic targets in breast cancer.

中文翻译：

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基于生物信息学和纳米粒子的联合研究揭示了ABCG2在乳腺癌抵抗中的作用。

背景技术ATP结合盒式亚家族G成员2（ABCG2）是一种半转运蛋白，在包括膀胱癌和肺癌在内的人类疾病中起关键作用，并且可能对化学疗法药物产生抗性。目的本研究旨在确定乳腺癌抗性蛋白（ABCG2）在乳腺癌中的作用和潜在机制。研究抑制ABCG2表达对乳腺癌细胞耐药性的逆转作用，为乳腺癌基因靶向治疗提供新思路。方法使用GeneCards和cBioPortal系统研究ABCG2的结构和基因组变异，以揭示ABCG2的遗传变异（包括扩增和深度缺失）。我们使用bc-GenExMiner 4.4中的数据进行了ABCG2表达与临床病理参数之间的相关性。然后，基于STRING，bc-GenExMiner 4.4和Enrichr数据库进行了ABCG2的蛋白质相互作用和功能富集分析。此外，我们使用GSCALite和PharmGKB分析了与ABCG2相互作用的基因的途径活性。使用磁性纳米粒子polyMAG作为ABCG2-siRNA的载体，将polyMAG-ABCG2-siRNA转染到抗阿霉素（DOX）的乳腺癌细胞系MCF-7 / ADR中，并直接转染到裸鼠的肿瘤中。专利US20150328485指出，磁性纳米颗粒可以附着于抗癌药，例如基于抗体的抗癌药。结果我们发现乳腺癌患者中ABCG2表达与临床病理参数（如雌激素受体（ER），孕激素受体（PR）和人表皮生长因子受体2（HER2））和淋巴结状态之间存在统计学意义的相关性。ABCG2与SLC2A9，KIT，ABCG1和MRPS7密切相关，这表明这些蛋白质可能是乳腺癌的功能伴侣。ABCG2的表达与多种致癌途径的激活或抑制相关。此外，我们发现ABCG2参与DOX信号通路。磁性纳米粒子携带的小干扰RNA（siRNA）可以减少ABCG2的表达，从而显着提高DOX对肿瘤的治疗效果。