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微小RNA-375-3p通过靶向肝细胞核因子-1β抑制喉鳞状细胞癌的进展。

miR-375-3p inhibits the progression of laryngeal squamous cell carcinoma by targeting hepatocyte nuclear factor-1β.

作者信息

Chang Kunpeng, Wei Zhenxing, Cao Hua

机构信息

Department of Otolaryngology Head and Neck Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, P.R. China.

Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

出版信息

Oncol Lett. 2020 Oct;20(4):80. doi: 10.3892/ol.2020.11941. Epub 2020 Aug 3.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is one of the most frequently diagnosed head and neck cancers worldwide. Increasing evidence suggests that microRNAs (miRNAs/miRs) regulate the progression of tumorigenesis and the malignant behaviors of cancer cells. The aim of this study was to investigate the function and underlying mechanism of miR-375-3p in LSCC. The expression of miR-375-3p in LSCC tissues and cells was detected using reverse transcription-quantitative PCR. The effects of miR-375-3p on the malignant phenotype of LSCC cells was determined using the Cell Counting Kit-8 assay and flow cytometry. The targets of miR-375-3p were predicted using the miRDB database and confirmed by the luciferase reporter assay. The results of the present study demonstrated that miR-375-3p was downregulated in LSCC tissues and cell lines. Furthermore, overexpression of miR-375-3p significantly suppressed the proliferation and cell cycle progression of LSCC cells. Overexpression of miR-375-3p also increased LSCC cell apoptosis. Mechanistical analysis indicated that miR-375-3p bound the 3'-untranslated region of the hepatocyte nuclear factor 1β (HNF1β) and decreased its expression in LSCC cells. Consistent with the role of HNF1β in glucose metabolism, overexpression of miR-375-3p significantly inhibited glucose consumption and lactate production in LSCC cells. Transfection with HNF1β notably reversed the inhibitory effect of miR-375-3p on the proliferation of LSCC cells. Collectively, these results indicate the tumor suppressive role of miR-375-3p in LSCC via HNF1β, suggesting that miR-375-3p may serve as a potential target in the treatment of LSCC.

摘要

喉鳞状细胞癌(LSCC)是全球最常被诊断出的头颈癌之一。越来越多的证据表明,微小RNA(miRNA/miR)可调节肿瘤发生的进程以及癌细胞的恶性行为。本研究旨在探究miR-375-3p在LSCC中的功能及潜在机制。采用逆转录定量PCR检测miR-375-3p在LSCC组织和细胞中的表达。使用细胞计数试剂盒-8检测法和流式细胞术确定miR-375-3p对LSCC细胞恶性表型的影响。利用miRDB数据库预测miR-375-3p的靶标,并通过荧光素酶报告基因检测进行验证。本研究结果表明,miR-375-3p在LSCC组织和细胞系中表达下调。此外,miR-375-3p的过表达显著抑制了LSCC细胞的增殖和细胞周期进程。miR-375-3p的过表达还增加了LSCC细胞的凋亡。机制分析表明,miR-375-3p与肝细胞核因子1β(HNF1β)的3'-非翻译区结合,并降低其在LSCC细胞中的表达。与HNF1β在葡萄糖代谢中的作用一致,miR-375-3p的过表达显著抑制了LSCC细胞的葡萄糖消耗和乳酸生成。转染HNF1β显著逆转了miR-375-3p对LSCC细胞增殖的抑制作用。总体而言,这些结果表明miR-375-3p通过HNF1β在LSCC中发挥肿瘤抑制作用,提示miR-375-3p可能成为LSCC治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3818/7436894/0f88914ba2ca/ol-20-04-11941-g00.jpg

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