miRNA-885-3p inhibits docetaxel chemoresistance in lung adenocarcinoma by downregulating Aurora A
miRNA-885-3p inhibits docetaxel chemoresistance in lung adenocarcinoma by downregulating Aurora A
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DOI：
10.3892/or.2018.6858
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发表时间：
2019-02-01
期刊：
影响因子：
4.2
通讯作者：
Chen, Longbang
中科院分区：
文献类型：
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作者：
Cao, Jiongrui;Geng, Jian;Chen, Longbang
Aurora A是有丝分裂丝氨酸/苏氨酸激酶家族的成员。它参与有丝分裂和减数分裂过程中的关键过程，Aurora A上调与恶性转化有关。在本研究中，我们发现Aurora A在耐紫杉醇的肺腺癌（LAD）细胞中的表达显著高于亲本细胞。Aurora A的高表达水平与LAD细胞的高耐药性和增殖显著相关，而沉默Aurora A通过下调NF-B和Bcl-2以及上调Bax表达促进caspase-3依赖的细胞凋亡。此外，由于Aurora A的抑制，观察到G2/M期细胞比例增加和S期细胞比例减少。此外，我们发现microRNA-885- 3 p（miR-885- 3 p）可以直接靶向Aurora A。miR-885- 3 p在紫杉醇耐药的LAD细胞中的表达显著低于亲本LAD细胞。miR-885- 3 p在体外可调节LAD细胞对多西他赛的反应、细胞增殖和凋亡。此外，我们发现Aurora A过表达或miR-885- 3 p抑制与LAD细胞中更具攻击性的行为相关。因此，miR-885- 3 p/Aurora A可能参与LAD细胞的化疗耐药性，评估miR-885- 3 p/Aurora A表达可能是指示对紫杉醇化疗敏感性的潜在方法。
Aurora A is a member of the mitotic serine/threonine kinase family. It is involved in key processes during mitosis and meiosis, and Aurora A upregulation is implicated in malignant transformation. In the present study, we revealed that Aurora A expression was significantly higher in docetaxel-resistant lung adenocarcinoma (LAD) cells than in parental cells. Higher levels of Aurora A expression were significantly correlated with higher chemoresistance and proliferation in LAD cells, while silencing Aurora A promoted caspase-3-dependent cell apoptosis by downregulating NF-B and Bcl-2 and upregulating Bax expression. In addition, an increased proportion of cells in the G2/M phase and a decreased proportion of cells in the S phase were observed due to the suppression of Aurora A. Furthermore, we identified that microRNA-885-3p (miR-885-3p) could target Aurora A directly. There was significantly lower miR-885-3p expression in docetaxel-resistant LAD cells than in parental LAD cells. miR-885-3p could modulate the docetaxel response, cell proliferation and apoptosis in LAD cells in vitro. Moreover, we found that Aurora A overexpression or miR-885-3p inhibition was associated with more aggressive behaviour in LAD cells. Thus, miR-885-3p/Aurora A may be involved in the chemoresistance of LAD cells, and assessing miR-885-3p/Aurora A expression may be a potential method for indicating chemosensitivity to docetaxel-based chemotherapy.