The treatment of triple-negative breast cancer (TNBC) relies largely on chemotherapies. However, it is frequent that TNBC patients develop resistance to the chemotherapy drugs. Generation of drug-resistant cell lines facilitates the identification of drug resistance. Here, we established two paclitaxel (PTX)-resistant TNBC cancer cell lines using an intermittent and stepwise method and found that long non-coding RNA long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) was significantly decreased in PTX-resistant cancer cells. Ectopic expression of LINC-PINT sensitized both PTX-resistant TNBC and wild-type TNBC to PTX. Moreover, RNA immunoprecipitation showed that LINC-PINT bound to RNA-binding protein NONO. Overexpression of LINC-PINT resulted in the degradation of NONO in a proteasome-dependent manner and vice versa. Knockdown of NONO with siRNA sensitized TNBC to PTX. We further analyzed the expression level of LINC-PINT and NONO in patient samples via online database and found that LINC-PINT and NONO may function antagonistically in all types of breast cancers. Taken together, our data illustrated a tumor suppressor role of LINC-PINT in sensitizing TNBC to chemotherapies via destabilizing NONO.

中文翻译：

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长的非编码RNA LINC-PINT通过靶向RNA结合蛋白NONO来减弱三阴性乳腺癌细胞中的紫杉醇耐药性。

三阴性乳腺癌（TNBC）的治疗主要依靠化学疗法。但是，TNBC患者经常对化疗药物产生耐药性。耐药细胞系的产生有助于鉴定耐药性。在这里，我们建立了两个使用间歇性和​​逐步方法的耐紫杉醇（PTX）的TNBC癌细胞系，发现长非编码RNA长基因间非编码RNA p53诱导的转录本（LINC-PINT）显着降低。耐PTX的癌细胞。LINC-PINT的异位表达使耐PTX的TNBC和野生型TNBC都对PTX敏感。此外，RNA免疫沉淀表明LINC-PINT与RNA结合蛋白NONO结合。LINC-PINT的过表达导致NONO以蛋白酶体依赖性方式降解，反之亦然。用siRNA抑制TNBC对PTX的NONO的抑制。我们通过在线数据库进一步分析了患者样品中LINC-PINT和NONO的表达水平，发现LINC-PINT和NONO在所有类型的乳腺癌中可能具有拮抗作用。两者合计，我们的数据说明了LINC-PINT在通过使NONO不稳定来使TNBC对化学疗法敏感的肿瘤抑制作用。