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NEAT1 mediates paclitaxel-resistance of non-small cell of lung cancer through activation of Akt/mTOR signalling pathway

机译:Neat1通过激活AKT / MTOR信号通路的激活介导肺癌非小细胞的紫杉醇抗性

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摘要

Development of paclitaxel-resistance is a main problem during non-small cell lung cancer (NSCLC) chemotherapy. Nuclear paraspeckle assembly transcript 1 (NEAT1) is an oncogenic long non-coding RNA (lncRNA) which has been proved to be aberrantly upregulated in many human malignancies. In this study, we investigated the mechanism by which NEAT1 contributed to paclitaxel-resistance in NSCLC. NEAT1 was upregulated significantly in paclitaxel-resistant NSCLC cell line, compared with other NSCLC cell lines and normal bronchial epithelial (BE) cell line. Knockdown of NEAT1 could reverse the paclitaxel-resistance through induction of apoptosis by increasing cleaved PARP and cleaved caspase-3 expression. Moreover, NEAT1 was associated with Akt/mTOR signalling pathway activation by increasing expression of p-Akt, p-mTOR, Bcl-2 and decreasing expression of Bax. In conclusion, these results demonstrated that NEAT1 underlay paclitaxel-resistance in NSCLC.
机译:紫杉醇抗性的发展是非小细胞肺癌(NSCLC)化疗期间的主要问题。 核ParaSpeckle组件转录物1(neat1)是一种致癌的长非编码RNA(LNCRNA),其已被证明在许多人类恶性肿瘤中被异常上调。 在这项研究中,我们研究了Neat1在NSCLC中对紫杉醇抗性有助于紫杉醇的机制。 与其他NSCLC细胞系和正常支气管上皮(BE)细胞系相比,在紫杉醇抗性NSCLC细胞系中显着上调整齐1。 Neat1的敲低可以通过增加切割的PARP和切割的caspase-3表达来诱导细胞凋亡来逆转紫杉醇抗性。 此外,通过增加P-AKT,P-MTOR,Bcl-2的表达和减少Bax表达,Neat1与Akt / mtor信号传导途径激活相关。 总之,这些结果表明NSCLC中的Neat1底层紫杉醇抗性。

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