Chemoresistance remains a major obstacle for improving the clinical outcome of patients with breast cancer. Recently, long noncoding RNAs (lncRNAs) have been implicated in breast cancer chemoresistance. However, the function and underlying mechanism are still largely unknown. Using lncRNA microarray, we identified 122 upregulated and 475 downregulated lncRNAs that might be related to the breast cancer chemoresistance. Among them, RP11-70C1.3 was one of the most highly expressed lncRNAs. In breast cancer patients, high RP11-70C1.3 expression predicted poor prognosis. Knockdown of RP11-70C1.3 inhibited the multidrug resistance of breast cancer cells in vitro and in vivo. Further investigations revealed that RP11-70C1.3 functioned as a competing endogenous RNA (ceRNA) for miR-6736-3p to increase NRP-1 expression. Notably, the rescue experiments showed that both miR-6736-3p inhibitor and NRP-1 overexpression could partly reverse the suppressive influence of RP11-70C1.3 knockdown on breast cancer chemoresistance. In conclusion, our study indicated that lncRNA RP11-70C1.3 regulated NRP-1 expression by sponging miR-6736-3p to confer chemoresistance of breast cancer cells. RP11-70C1.3 might be a potential therapeutic target in enhancing the clinical efficacy of chemotherapy in breast cancer.

中文翻译：

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长链非编码 RNA RP11-70C1.3 通过 miR-6736-3p/NRP-1 轴赋予乳腺癌细胞的化学抗性。

化疗耐药性仍然是改善乳腺癌患者临床结果的主要障碍。最近，长链非编码 RNA (lncRNA) 与乳腺癌化疗耐药有关。然而，其功能和潜在机制仍然很大程度上未知。使用 lncRNA 微阵列，我们鉴定了 122 个上调和 475 个下调的 lncRNA，这些 lncRNA 可能与乳腺癌化疗耐药性有关。其中，RP11-70C1.3是表达量最高的lncRNA之一。在乳腺癌患者中，RP11-70C1.3 高表达预示预后不良。RP11-70C1.3 的敲低在体外和体内抑制了乳腺癌细胞的多药耐药性。进一步的研究表明，RP11-70C1.3 作为 miR-6736-3p 的竞争性内源性 RNA (ceRNA) 可增加 NRP-1 的表达。尤其，拯救实验表明，miR-6736-3p抑制剂和NRP-1过表达都可以部分逆转RP11-70C1.3敲低对乳腺癌化疗耐药的抑制作用。总之，我们的研究表明，lncRNA RP11-70C1.3 通过海绵化 miR-6736-3p 来调节 NRP-1 的表达，从而赋予乳腺癌细胞的化学抗性。RP11-70C1.3可能是提高乳腺癌化疗临床疗效的潜在治疗靶点。