Department of Thyroid and Breast Surgery, The First People's Hospital of Shangqiu, Shangqiu, China.
Department of Oncology, The First People's Hospital of Shangqiu, Shangqiu, China.
J Cell Mol Med. 2018 Sep;22(9):4068-4075. doi: 10.1111/jcmm.13679. Epub 2018 Jul 3.
Emerging evidence has indicated the important function of long non-coding RNAs (lncRNAs) in tumour chemotherapy resistance. However, the underlying mechanism is still ambiguous. In this study, we investigate the physiopathologic role of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) on the paclitaxel (PTX) resistance in breast cancer. Results showed that lncRNA FTH1P3 was up-regulated in paclitaxel-resistant breast cancer tissue and cells (MCF-7/PTX and MDA-MB-231/PTX cells) compared with paclitaxel-sensitive tissue and parental cell lines (MCF-7, MDA-MB-231). Gain- and loss-of-function experiments revealed that FTH1P3 silencing decreased the 50% inhibitory concentration (IC50) value of paclitaxel and induced cell cycle arrest at G2/M phase, while FTH1P3-enhanced expression exerted the opposite effects. In vivo, xenograft mice assay showed that FTH1P3 silencing suppressed the tumour growth of paclitaxel-resistant breast cancer cells and ABCB1 protein expression. Bioinformatics tools and luciferase reporter assay validated that FTH1P3 promoted ABCB1 protein expression through targeting miR-206, acting as a miRNA "sponge." In summary, our results reveal the potential regulatory mechanism of FTH1P3 on breast cancer paclitaxel resistance through miR-206/ABCB1, providing a novel insight for the breast cancer chemoresistance.
新出现的证据表明，长非编码 RNA（lncRNA）在肿瘤化疗耐药中具有重要功能。然而，其潜在机制仍不清楚。在这项研究中，我们研究了 lncRNA 铁蛋白重链 1 假基因 3（FTH1P3）在乳腺癌紫杉醇（PTX）耐药中的病理生理作用。结果表明，lncRNA FTH1P3 在紫杉醇耐药的乳腺癌组织和细胞（MCF-7/PTX 和 MDA-MB-231/PTX 细胞）中上调，与紫杉醇敏感的组织和亲本细胞系（MCF-7、MDA-MB-231）相比。增益和功能丧失实验表明，FTH1P3 沉默降低了紫杉醇的 50%抑制浓度（IC50）值，并诱导细胞周期停滞在 G2/M 期，而 FTH1P3 增强表达则产生相反的效果。在体内，异种移植小鼠实验表明，FTH1P3 沉默抑制了紫杉醇耐药乳腺癌细胞的肿瘤生长和 ABCB1 蛋白表达。生物信息学工具和荧光素酶报告基因实验验证了 FTH1P3 通过靶向 miR-206 促进 ABCB1 蛋白表达，充当 miRNA“海绵”。总之，我们的研究结果揭示了 FTH1P3 通过 miR-206/ABCB1 对乳腺癌紫杉醇耐药的潜在调节机制，为乳腺癌的化疗耐药提供了新的见解。
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