LncRNA LINP1 confers tamoxifen resistance and negatively regulated by ER signaling in breast cancer
LncRNA LINP1 confers tamoxifen resistance and negatively regulated by ER signaling in breast cancer
复制标题
LncRNA LINP1 在乳腺癌中赋予他莫昔芬耐药性并受到 ER 信号传导的负调控
DOI：
10.1016/j.cellsig.2020.109536
复制
发表时间：
2020-04-01
影响因子：
4.8
通讯作者：
Yang, Qifeng
中科院分区：
文献类型：
--
作者：
Ma, Tingting;Liang, Yiran;Yang, Qifeng
他莫昔芬（TAM）经常用于治疗雌激素受体阳性（ER+）乳腺癌患者;然而，内分泌耐药性的发展是成功治疗的主要障碍。最近的研究表明，长链非编码RNA（lncRNA）可能在调节乳腺癌的内分泌抵抗中起关键作用。在本研究中，它被确定，在非同源末端连接途径1（LINP 1）中的lncRNA的表达在他莫昔芬耐药的乳腺癌细胞中增加，并且LINP 1敲低显着减弱了他莫昔芬耐药性和他莫昔芬耐药的乳腺癌细胞在体外和体内的活力。LINP 1敲低增加了用他莫昔芬处理后的细胞凋亡。此外，LINP 1过表达通过调节EMT过程导致细胞迁移率增加。从机制上讲，LINP 1是ER介导的转录抑制的直接靶点，他莫昔芬治疗和激素剥夺都增加了LINP 1的表达。LINP 1过表达与ER蛋白水平下调相关，并减弱了雌激素反应，这是抗雌激素抵抗的关键因素。总之，本研究强调了LINP 1在他莫昔芬耐药性中的关键作用，这可能是提高他莫昔芬治疗乳腺癌有效性和疗效的潜在靶点。
Tamoxifen (TAM) is frequently used to treat patients with estrogen receptor-positive (ER+ ) breast cancer; however, the development of endocrine resistance represents a major impediment for successful treatment. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) may serve critical roles in regulating endocrine resistance in breast cancer. In the present study, it was determined that the expression of lncRNA in nonhomologous end joining pathway 1 (LINP1) was increased in tamoxifen-resistant breast cancer cells, and that LINP1 knockdown significantly attenuated the tamoxifen resistance and viability of tamoxifen-resistant breast cancer cells in vitro and in vivo. LINP1 knockdown increased apoptosis in cells following treatment with tamoxifen. Furthermore, LINP1 overexpression resulted in increased cell mobility by regulating the EMT process. Mechanistically, LINP1 is a direct target of ER-mediated transcriptional repression, and both tamoxifen treatment and hormone deprivation increased the expression of LINP1. LINP1 overexpression was associated with downregulation of the levels of ER protein and attenuated the estrogen response, which is a pivotal contributing factor to anti-estrogen resistance. Taken together, the present study highlights the pivotal role of LINP1 in tamoxifen resistance, which may serve as a potential target to improve the effectiveness and efficacy of tamoxifen treatment in breast cancer.