Next generation deep sequencing identified a novel lncRNA n375709 associated with paclitaxel resistance in nasopharyngeal carcinoma

Next generation deep sequencing identified a novel lncRNA n375709 associated with paclitaxel resistance in nasopharyngeal carcinoma
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下一代深度测序鉴定出与鼻咽癌紫杉醇耐药相关的新型 lncRNA n375709

DOI:
10.3892/or.2016.4981
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发表时间:
2016-10-01
期刊:
影响因子:
4.2
通讯作者:
Wang, Yunyun
Wang, Yunyun
中科院分区:
医学3区
文献类型:
--
作者:
Ren, Shuling;Li, Guo;Wang, Yunyun

文献摘要

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紫杉醇耐药是制约鼻咽癌疗效和预后的重要因素。越来越多的证据表明,长链非编码RNA(lncRNA)的异常表达有助于癌症的进展。因此,我们的目的是确定与鼻咽癌紫杉醇耐药相关的lncRNA。首先,成功地建立了紫杉醇耐药CNE-2细胞(CNE-2-Pr),并证实其耐药性是亲本CNE-2细胞的33.26 ± 8.70倍。然后,通过下一代测序技术构建了与NPC紫杉醇耐药相关的lncRNA差异表达谱,其中包含总共2,670个已知lncRNA和4,820个新lncRNA。我们的qRT-PCR证实,前8个lncRNA中有7个以与预测相同的趋势表达,包括4个已知的lncRNA(n375709,n377806,n369241和n335785)和3个新的lncRNA(Unigene6646,Unigene6644和Unigene1654)。我们的小组最初专注于lncRNA n375709,这是已知lncRNA中最显著过表达的lncRNA。CCK-8测定表明,进一步抑制lncRNA n375709增加了NPC 5 - 8F和6 - 10B细胞对紫杉醇的敏感性。总之,本研究提供了与紫杉醇耐药相关的lncRNA表达谱的概述。lncRNA n375709被鉴定为参与NPC紫杉醇抗性的调节。
Paclitaxel chemoresistance restricts the therapeutic efficacy and prognosis of patients with nasopharyngeal carcinoma (NPC). Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) contributes to cancer progression. Therefore, we aimed to identify lncRNAs associated with paclitaxel resistance in NPC. First, paclitaxel-resistant CNE-2 cells (CNE-2-Pr) were successfully established and confirmed to be 33.26±8.70 times more resistant than parental CNE-2 cells. Then, differential expression profile of lncRNAs associated with NPC paclitaxel resistance, which contained a total of 2,670 known lncRNAs and 4,820 novel lncRNAs, was constructed via next generation sequencing technology. Our qRT-PCR confirmed that 7 of the top 8 lncRNAs were expressed with the same trend as the prediction, including 4 known lncRNAs (n375709, n377806, n369241 and n335785) and 3 novel lncRNAs (Unigene6646, Unigene6644 and Unigene1654). Our group initially focused on lncRNA n375709, which was the most significantly overexpressed lncRNA of the known lncRNAs. CCK-8 assays demonstrated that further inhibition of lncRNA n375709 increased the paclitaxel sensitivity in NPC 5-8F and 6-10B cells. In conclusion, the present study provided an overview of the expression profiles of lncRNAs correlated with paclitaxel resistance. lncRNA n375709 was identified to be involved in the regulation of NPC paclitaxel resistance.