Long noncoding RNA SFTA1P promoted apoptosis and increased cisplatin chemosensitivity via regulating the hnRNP-U-GADD45A axis in lung squamous cell carcinoma.

Long noncoding RNA SFTA1P promoted apoptosis and increased cisplatin chemosensitivity via regulating the hnRNP-U-GADD45A axis in lung squamous cell carcinoma.
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长非编码RNA SFTA1P通过调节肺鳞状细胞癌中的hnRNP-U-GADD45A轴促进细胞凋亡并增加顺铂化疗敏感性

DOI:
10.18632/oncotarget.22138
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发表时间:
2017-11-14
期刊:
影响因子:
--
通讯作者:
Liu ZQ
Liu ZQ
中科院分区:
其他
文献类型:
--
作者:
Li L;Yin JY;He FZ;Huang MS;Zhu T;Gao YF;Chen YX;Zhou DB;Chen X;Sun LQ;Zhang W;Zhou HH;Liu ZQ

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化疗不敏感一直是肺鳞状细胞癌临床治疗的主要障碍之一。最近,越来越多的证据表明,长的非编码RNA(LncRNAs)在许多癌症类型中促进肿瘤的发生。然而,lncRNAs在顺铂治疗中的潜在生物学作用和调控机制还知之甚少。在这里,我们发现在肺组织中高表达的lncRNA SFTA1P(表面活性物质相关1,假基因)在LSCC组织中表达下调,并可在顺铂诱导的LSCC细胞中表达。SFTA1P升高可诱导LSCC细胞凋亡,增强其对顺铂的敏感性。我们进一步发现hnRNP-U(异质性核糖核蛋白U)在喉鳞状细胞癌中表达下调,并与患者的不良预后以及SFTA1P呈正相关。机制研究表明,SFTA1P可上调hnRNP-U的表达。此外,我们还发现hnRNP-U通过上调GADD45A的表达来增强顺铂诱导的细胞凋亡,GADD45A的高表达与喉癌患者良好的预后相关。我们的研究结果表明,SFTA1P可作为喉癌诊断的有用生物标志物和预测顺铂化疗疗效的指标。
Chemotherapeutic insensitivity remains one of the major obstacles in clinical treatment of lung squamous cell carcinoma (LSCC). Recently, increasing evidence has suggested that long non-coding RNAs (lncRNAs) promote tumorigenesis in many cancer types. However, the potential biological roles and regulatory mechanisms of lncRNAs in response to cisplatin treatment are poorly understood. Here, we found that lncRNA SFTA1P (surfactant associated 1, pseudogene), highly expressed in lung, was down-regulated in LSCC tissues and could be induced upon cisplatin treatment in LSCC cells. Elevated SFTA1P induced apoptosis and enhanced the sensitivity to cisplatin of LSCC cells. We further identified that hnRNP-U (heterogeneous nuclear ribonucleoprotein U) was down-regulated in LSCCs and positively correlated with patients’ poor prognosis as well as SFTA1P. Mechanistic studies revealed that SFTA1P could up-regulate hnRNP-U expression. In addition, we identified that hnRNP-U enhanced cisplatin-induced apoptosis through up-regulation of GADD45A, high expression of which was correlated with good prognosis in LSCC patients. Our findings demonstrated that SFTA1P might serve as a useful biomarker for LSCC diagnosis and a predictor for cisplatin chemotherapy response in patients with LSCC.
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