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沉默长链非编码RNA NEAT1可增强顺铂化疗对膀胱癌细胞生长、侵袭及凋亡的抑制作用。

Silencing long non-coding RNA NEAT1 enhances the suppression of cell growth, invasion, and apoptosis of bladder cancer cells under cisplatin chemotherapy.

作者信息

Zhao Wenchao, Li Wenqi, Jin Xin, Niu Tianli, Cao Yuanfei, Zhou Peng, Zheng Minghua

机构信息

Department of Urology, Taizhou People's Hospital Taizhou, Jiangsu, P. R. China.

Department of Quality Control, Taizhou People's Hospital Taizhou, Jiangsu, P. R. China.

出版信息

Int J Clin Exp Pathol. 2019 Feb 1;12(2):549-558. eCollection 2019.

Abstract

It has been proven that NEAT1 as a long non-coding RNA (lncRNA) is highly expressed in bladder cancer (BC). Nevertheless, the oncogenic roles of NEAT1 in BC remain largely unknown. In the present study, we observed that the RNA level of NEAT1.1, one RNA variant of NEAT1, was reduced in cisplatin-sensitive T24 cells compared to cisplatin-resistant T24 (T24R) cells after both treated with cisplatin modulated through Wnt/β-catenin signaling pathway using RNA-seq. Furthermore, NEAT1.1 was knocked down within T24R cells and caused a phenotype of the compromised cell growth, invasion and enhanced apoptosis upon cisplatin treatment compared to untreated T24R cells. Finally, c-MYC, OCT4 and p53 were determined to contribute to the transcriptional regulation of NEAT1.1 under cisplatin using ChIP assay. Taken together, our results suggest that NEAT1.1 blocking can promote the effect of cisplatin for BC treatment.

摘要

已有研究证明,长链非编码RNA(lncRNA)NEAT1在膀胱癌(BC)中高表达。然而,NEAT1在BC中的致癌作用仍不清楚。在本研究中,我们通过RNA测序观察到,在用Wnt/β-连环蛋白信号通路调节顺铂处理后,与顺铂耐药的T24(T24R)细胞相比,顺铂敏感的T24细胞中NEAT1的一种RNA变体NEAT1.1的RNA水平降低。此外,在T24R细胞中敲低NEAT1.1,与未处理的T24R细胞相比,顺铂处理后导致细胞生长、侵袭受损和凋亡增加的表型。最后,通过染色质免疫沉淀法(ChIP)确定c-MYC、OCT4和p53在顺铂作用下对NEAT1.1的转录调控有作用。综上所述,我们的结果表明,阻断NEAT1.1可以增强顺铂对BC的治疗效果。

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