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miR-143-3p 通过靶向 Bcl-2 和 IGF1R 抑制鼻鳞状细胞癌的进展。

MiR-143-3p suppresses the progression of nasal squamous cell carcinoma by targeting Bcl-2 and IGF1R.

机构信息

Department of Family Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Department of Otorhinolaryngology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Otorhinolaryngology, Affiliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Biochem Biophys Res Commun. 2019 Oct 20;518(3):492-499. doi: 10.1016/j.bbrc.2019.08.075. Epub 2019 Aug 20.

DOI:10.1016/j.bbrc.2019.08.075
PMID:31443963
Abstract

Dysregulated microRNAs (miRNAs) play crucial roles in the occurrence and development of multiple tumours, but their roles in the progression of nasal squamous cell carcinoma (NSCC) remain unknown. The aim of our study was to investigate the potential function and molecular mechanism of miR-143-3p in NSCC. Expression of miRNA and mRNA was detected by quantitative real-time reverse transcription-PCR (qRT-PCR). Forced overexpression of miR-143-3p was established by transfecting mimics into NSCC cell line. Then, we investigated the role of miR-143-3p in human NSCC cell proliferation, apoptosis, cycle and migration by using MTT, flow cytometry and transwell assays. Bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter analysis were performed to validate the relationship between miR-143-3p and its potential targets. We found that miR-143-3p was substantially downregulated in human NSCC tissues and cell line. Forced upregulation of miR-143-3p significantly attenuated cell proliferation and migration. Furthermore, this change could induce apoptosis and G1-phase arrest of NSCC cells. Mechanistically, miR-143-3p directly targeted and significantly suppressed Bcl-2 and IGF1R expression. In summary, miR-143-3p regulation of the proliferation, apoptosis, cell cycle and migration of NSCC probably partly depends on inhibition of Bcl-2 and IGF1R, indicating that miR-143-3p may be a novel molecular therapeutic target for NSCC.

摘要

失调的 microRNAs(miRNAs)在多种肿瘤的发生和发展中发挥着关键作用,但它们在鼻鳞状细胞癌(NSCC)进展中的作用尚不清楚。本研究旨在探讨 miR-143-3p 在 NSCC 中的潜在功能和分子机制。采用实时定量逆转录 PCR(qRT-PCR)检测 miRNA 和 mRNA 的表达。通过转染 mimics 建立 miR-143-3p 的过表达。然后,通过 MTT、流式细胞术和 Transwell 检测研究 miR-143-3p 对人 NSCC 细胞增殖、凋亡、周期和迁移的作用。通过生物信息学分析、qRT-PCR、Western blot 和荧光素酶报告分析验证 miR-143-3p 与其潜在靶标的关系。我们发现 miR-143-3p 在人 NSCC 组织和细胞系中明显下调。miR-143-3p 的强制上调显著减弱了细胞增殖和迁移。此外,这种变化可诱导 NSCC 细胞凋亡和 G1 期阻滞。机制上,miR-143-3p 直接靶向并显著抑制 Bcl-2 和 IGF1R 的表达。总之,miR-143-3p 对 NSCC 增殖、凋亡、细胞周期和迁移的调节可能部分依赖于对 Bcl-2 和 IGF1R 的抑制,表明 miR-143-3p 可能是 NSCC 的一种新的分子治疗靶点。

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