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微小RNA-92b通过靶向鼻咽癌中的Smad3抑制上皮-间质转化诱导的迁移和侵袭。

MicroRNA-92b inhibits epithelial-mesenchymal transition-induced migration and invasion by targeting Smad3 in nasopharyngeal cancer.

作者信息

Zhao Chong, Zhao Feipeng, Feng Huajun, Xu Shengen, Qin Gang

机构信息

Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China.

出版信息

Oncotarget. 2017 Sep 27;8(53):91603-91613. doi: 10.18632/oncotarget.21342. eCollection 2017 Oct 31.

Abstract

Increasing studies reports that aberrant miRNAs contribute to nasopharyngeal carcinoma (NPC) development and progression. However, the role of miR-92b in NPC remains unclear. In present research, we found that a reduced miR-92b expression in NPC tissues and cell lines. The clinical data showed that the down-regulated miR-92b expression was obviously associated with adverse prognostic characteristic. Furthermore, we confirmed that miR-92b was a novel independent prognostic symbol for predicting 5-year survival of NPC patients. MiR-92b overexpression inhibited cell migration, invasion and EMT progress, while down-regulated miR-92b reversed the effect. Besides, miR-92b could modulate Smad3 by directly binding to its 3'-UTR. In clinical samples of NPC, miR-92b inversely correlated with Smad3. Alternation of Smad3 expression at least partially abrogated the migration, invasion and EMT progress of miR-92b on NPC cells. In summary, our results indicated that miR-92b functioned as a tumor suppressor gene in regulating the EMT and metastasis of NPC via targeting Smad3, and may represent a novel potential therapeutic target and prognostic marker for NPC.

摘要

越来越多的研究报道,异常的微小RNA(miRNA)促进鼻咽癌(NPC)的发生和发展。然而,miR-92b在鼻咽癌中的作用仍不清楚。在本研究中,我们发现鼻咽癌组织和细胞系中miR-92b表达降低。临床数据显示,miR-92b表达下调与不良预后特征明显相关。此外,我们证实miR-92b是预测鼻咽癌患者5年生存率的一个新的独立预后指标。miR-92b过表达抑制细胞迁移、侵袭和上皮-间质转化(EMT)进程,而下调miR-92b则逆转该效应。此外,miR-92b可通过直接结合Smad3的3'-非翻译区(3'-UTR)来调节Smad3。在鼻咽癌临床样本中,miR-92b与Smad3呈负相关。Smad3表达的改变至少部分消除了miR-92b对鼻咽癌细胞迁移、侵袭和EMT进程的影响。总之,我们的结果表明,miR-92b通过靶向Smad3在调节鼻咽癌的EMT和转移中起肿瘤抑制基因的作用,并且可能代表鼻咽癌一个新的潜在治疗靶点和预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1178/5710950/bfef653c73b7/oncotarget-08-91603-g001.jpg

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