Breast cancer is one of the most prevalent cancers in women. Chemoresistance is a major obstacle for the treatment of breast cancer. We investigated the role of long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) in paclitaxel (PTX) resistance in breast cancer. CASC2 expression was increased in PTX-resistant clinical samples and cell lines. PTX induced CASC2 expression in a concentration-dependent manner. Downregulation of CASC2 increased PTX toxicity and decreased IC50 value, while upregulation of CASC2 decreased PTX toxicity and increased IC50 value in MCF-7/PTX and MDA-MB-231/PTX cells. Moreover, downregulation of CASC2 decreased tumor growth in xenograft mice implanted with MCF-7/PTX cells. miR-18a-5p possessed a putative binding site in 3'-UTR of CASC2 and cyclin-dependent kinase 19 (CDK19). In PTX-resistant breast cancer cells, miR-18a-5p expression was decreased. CASC2 and miR-18a-5p could negatively regulate the expression of each other. CDK19 expression could be negatively regulated by miR-18a-5p, but positively regulated by CASC2. miR-18a-5p mimics or downregulation of CDK19 decreased tumor growth in xenograft mice implanted with MCF-7/PTX cells. In summary, we identified that CASC2 activated PTX resistance in breast cancer through regulation of miR-18a-5p/CDK19. We highlight the importance of CASC2/miR-18a-5p/CDK19 axis in the chemoresistance of breast cancer and provide potential targets for the improving chemotherapy of breast cancer.

中文翻译：

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较长的非编码RNA CASC2通过调节miR-18a-5p / CDK19促进乳腺癌中的紫杉醇耐药性。

乳腺癌是女性中最普遍的癌症之一。化学抗性是治疗乳腺癌的主要障碍。我们调查了长期非编码RNA（lncRNA）癌症易感性候选物2（CASC2）在乳腺癌中对紫杉醇（PTX）的耐药性中的作用。在耐PTX的临床样品和细胞系中，CASC2表达增加。PTX以浓度依赖性方式诱导CASC2表达。在MCF-7 / PTX和MDA-MB-231 / PTX细胞中，CASC2的下调会增加PTX毒性并降低IC50值，而CASC2的上调会降低PTX毒性并增加IC50值。此外，CASC2的下调降低了植入MCF-7 / PTX细胞的异种移植小鼠的肿瘤生长。miR-18a-5p在CASC2的3'-UTR和细胞周期蛋白依赖性激酶19（CDK19）中具有假定的结合位点。在耐PTX的乳腺癌细胞中，miR-18a-5p表达降低。CASC2和miR-18a-5p可能彼此负调控。CDK19的表达可能受miR-18a-5p的负调控，但受CASC2的正调控。在植入MCF-7 / PTX细胞的异种移植小鼠中，miR-18a-5p的模拟或CDK19的下调降低了肿瘤的生长。总之，我们确定了CASC2通过调节miR-18a-5p / CDK19激活了乳腺癌中的PTX耐药性。我们强调了CASC2 / miR-18a-5p / CDK19轴在乳腺癌化学耐药性中的重要性，并为改善乳腺癌的化学疗法提供了潜在的靶标。但受到CASC2的积极调控。在植入MCF-7 / PTX细胞的异种移植小鼠中，miR-18a-5p的模拟或CDK19的下调降低了肿瘤的生长。总之，我们确定了CASC2通过调节miR-18a-5p / CDK19激活了乳腺癌中的PTX耐药性。我们强调了CASC2 / miR-18a-5p / CDK19轴在乳腺癌化学耐药性中的重要性，并为改善乳腺癌的化学疗法提供了潜在的靶标。但受到CASC2的积极调控。在植入MCF-7 / PTX细胞的异种移植小鼠中，miR-18a-5p的模拟或CDK19的下调降低了肿瘤的生长。总之，我们确定了CASC2通过调节miR-18a-5p / CDK19激活了乳腺癌中的PTX耐药性。我们强调了CASC2 / miR-18a-5p / CDK19轴在乳腺癌化学耐药性中的重要性，并为改善乳腺癌的化学疗法提供了潜在的靶标。