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lncRNA ZFAS1 的敲低通过海绵吸附 miR-135a 抑制鼻咽癌的进展。

Knockdown of lncRNA ZFAS1 inhibits progression of nasopharyngeal carcinoma by sponging miR-135a.

机构信息

Department of Otorhinolaryngology, Xingtai People's Hospital, Xingtai, China.

Department of Internal Medicine, Xingtai County Central Hospital, Xingtai, China.

出版信息

Neoplasma. 2019 Jun 29;66(6):939-945. doi: 10.4149/neo_2018_181213N963. Print 2019 Nov.

Abstract

Nasopharyngeal carcinoma (NPC) is one common head and neck malignancy with leading cause of cancer-related death. Long noncoding RNAs (lncRNAs) have been reported to play essential roles in progression, prognosis and treatment of NPC. However, the exact role of lncRNA zinc finger antisense 1 (ZFAS1) in NPC progression and its potential mechanism remain largely unknown.The expressions of ZFAS1 and microRNA-135a (miR-135a) were measured in NPC tissues or cells by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between ZFAS1 and miR-135a was explored by luciferase reporter assay and RNA immunoprecipitation (RIP). Cell proliferation, apoptosis, migration and invasion were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5 -diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry or trans-well assay, respectively. Our data showed the expression of ZFAS1 was up-regulated and miR-135a was down-regulated in NPC tissues and cells. miR-135a was bound to ZFAS1 in NPC cells. Moreover, knockdown of ZFAS1 or addition of miR-135a inhibited cell proliferation, migration and invasion but promoted apoptosis in NPC cells. Besides, down-regulation of miR-135a reversed abrogation of ZFAS1-mediated inhibition of proliferation, migration and invasion and increase of apoptosis in NPC cells. Our data suggested Inhibition of ZFAS1 protected against proliferation, migration and invasion but contributed to apoptosis by sponging miR-135a in NPC cells, providing a novel avenue for NPC treatment.

摘要

鼻咽癌(NPC)是一种常见的头颈部恶性肿瘤,是癌症相关死亡的主要原因。长链非编码 RNA(lncRNA)已被报道在 NPC 的进展、预后和治疗中发挥重要作用。然而,lncRNA 锌指反义 1(ZFAS1)在 NPC 进展中的确切作用及其潜在机制在很大程度上仍不清楚。通过实时定量聚合酶链反应(qRT-PCR)测量 NPC 组织或细胞中 ZFAS1 和 microRNA-135a(miR-135a)的表达。通过荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)实验探索 ZFAS1 和 miR-135a 之间的相互作用。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐(MTT)测定、流式细胞术或 Transwell 测定分别分析细胞增殖、凋亡、迁移和侵袭。我们的数据显示,ZFAS1 的表达在 NPC 组织和细胞中上调,miR-135a 的表达下调。miR-135a 与 NPC 细胞中的 ZFAS1 结合。此外,ZFAS1 的敲低或 miR-135a 的添加抑制 NPC 细胞的增殖、迁移和侵袭,但促进细胞凋亡。此外,下调 miR-135a 逆转了 ZFAS1 介导的抑制增殖、迁移和侵袭以及增加 NPC 细胞凋亡的作用。我们的数据表明,抑制 ZFAS1 通过海绵 miR-135a 来保护 NPC 细胞免受增殖、迁移和侵袭的侵害,但促进细胞凋亡,为 NPC 的治疗提供了一个新的途径。

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