Long noncoding RNA (lncRNA) differentiation antagonizing noncoding RNA (DANCR) is overexpressed in human triple-negative breast cancer (TNBC) and promotes cell migration and proliferation. TNBC is limited in treatment options relative to hormone-receptor-positive breast cancer and is commonly treated with chemotherapy, which is often compromised by acquired resistance. DANCR has been implicated in the development of chemoresistance across multiple cancer types. Here, we applied magnetic resonance molecular imaging (MRMI) with a targeted contrast agent, MT218, specific to extradomain-B fibronectin (EDB-FN), a marker for epithelial-to-mesenchymal transition, to assess the therapeutic efficacy of the combination of paclitaxel and ZD2-PEG-ECO/siDANCR nanoparticles (ZD2-siDANCR-ELNP) to treat TNBC. The treatment of orthotopic MDA-MB-231 TNBC in mice with paclitaxel significantly suppressed tumor growth but with a significant increase of EDB-FN in the tumor, as revealed by MRMI and immunohistochemistry. Combining ZD2-siDANCR-ELNP with paclitaxel further reduced tumor sizes, along with reduced EDB-FN expression. Interestingly, MT218-MRMI revealed a lower reduction of tumor signal enhancement with the combination treatment than that with the siDANCR treatment alone, which was supported by higher cell density in the tumors treated with the combination therapy, as shown by histochemical analysis. MT218-MRMI clearly revealed the changes of the tumor microenvironment in response to various therapies and is effective to noninvasively assess the response of TNBC tumors to the therapies. Regulating oncogenic lncRNA DANCR is an effective strategy for improving the outcomes of chemotherapy in TNBC.

中文翻译：

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利用磁共振分子成像评估 lncRNA DANCR 的 RNAi 与化疗联合治疗三阴性乳腺癌的疗效

长非编码 RNA (lncRNA) 分化拮抗非编码 RNA (DANCR) 在人类三阴性乳腺癌 (TNBC) 中过度表达，并促进细胞迁移和增殖。与激素受体阳性乳腺癌相比，TNBC 的治疗选择有限，通常采用化疗治疗，而化疗往往会受到获得性耐药的影响。 DANCR 与多种癌症类型的化疗耐药性的发展有关。在这里，我们应用磁共振分子成像 (MRMI) 和靶向造影剂 MT218（针对上皮间质转化标记物外域 B 纤连蛋白 (EDB-FN)）进行特异性治疗，以评估联合治疗的治疗效果。紫杉醇和 ZD2-PEG-ECO/siDANCR 纳米颗粒 (ZD2-siDANCR-ELNP) 治疗 TNBC。 MRMI 和免疫组织化学显示，用紫杉醇对小鼠进行原位 MDA-MB-231 TNBC 治疗可显着抑制肿瘤生长，但肿瘤中的 EDB-FN 显着增加。 ZD2-siDANCR-ELNP 与紫杉醇的组合进一步减小了肿瘤大小，同时减少了 EDB-FN 表达。有趣的是，MT218-MRMI 显示，与单独使用 siDANCR 治疗相比，联合治疗组肿瘤信号增强的减少程度较低，组织化学分析显示，联合治疗组治疗的肿瘤中细胞密度较高，支持了这一点。 MT218-MRMI清楚地揭示了肿瘤微环境对各种治疗的反应变化，可有效无创评估TNBC肿瘤对治疗的反应。调节致癌lncRNA DANCR是改善TNBC化疗结果的有效策略。