Department of Oncology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523000, Guangdong Province, P.R. China.
Clinical Research Center, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523000, Guangdong Province, P.R. China.
Aging (Albany NY). 2020 May 27;12(10):8893-8912. doi: 10.18632/aging.103012.
Chemoresistance remains a significant obstacle for effective adriamycin (ADR) treatment in breast cancer. Recent efforts have revealed that long noncoding RNAs (lncRNAs) play a crucial role in cancer biology, including chemoresistance. We identified the lncRNA LOC645166 was upregulated in adriamycin resistant-breast cancer cells by Microarray analysis, which was further confirmed in the tissues of nonresponsive patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical assays. Downregulation of lncRNA LOC645166 increased cell sensitivity to adriamycin both and . In contrast, upregulation of lncRNA LOC645166 strengthened the tolerance of breast cancer cells to adriamycin. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. Together, the present study suggested that lncRNA LOC645166 mediated adriamycin chemoresistance in breast cancer by regulating GATA3 via NF-κB.
化疗耐药性仍然是乳腺癌中阿霉素（ADR）有效治疗的重大障碍。最近的研究表明，长非编码 RNA（lncRNA）在癌症生物学中发挥着关键作用，包括化疗耐药性。我们通过微阵列分析发现 lncRNA LOC645166 在阿霉素耐药乳腺癌细胞中上调，通过逆转录-定量聚合酶链反应（RT-qPCR）、Western blot 和免疫组织化学检测进一步在无反应患者的组织中得到证实。lncRNA LOC645166 的下调增加了细胞对阿霉素的敏感性。相比之下，lncRNA LOC645166 的上调增强了乳腺癌细胞对阿霉素的耐受性。染色质免疫沉淀（ChIP）和 RNA 结合蛋白免疫沉淀（RIP）表明，lncRNA LOC645166 可以通过与核因子 kappa-轻链增强子的 B 细胞激活因子（NF-κB）结合，增加 GATA 结合蛋白 3（GATA3）的表达，从而激活 STAT3 并促进乳腺癌的化疗耐药性。总之，本研究表明，lncRNA LOC645166 通过 NF-κB 调节 GATA3 介导乳腺癌的阿霉素耐药性。
