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下调 miR-21 可调节 Ras 表达,促进喉鳞状细胞癌细胞凋亡并抑制其侵袭。

Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma.

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China.

出版信息

Eur J Cancer. 2010 Dec;46(18):3409-16. doi: 10.1016/j.ejca.2010.07.047.

DOI:10.1016/j.ejca.2010.07.047
PMID:20801640
Abstract

MiRNAs are small, noncoding RNA molecules that emerge as important regulators of cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally related to cellular proliferation and apoptosis. In this study, we found that miR-21 is overexpressed in Laryngeal squamous cell carcinoma (LSCC) and correlated with advanced stage. Inhibition of miR-21 by antisense oligonucleotides (ASO) led to decreased protein level of Ras and profound suppression of cell proliferation and invasion. Hep-2 cells exposed to miR-21 ASO exhibited cell cycle arrest at G1 phase and increased apoptosis. Furthermore, growth of LSCC xenograft tumours was significantly suppressed by repeated injection of ASO-miR-21 lentivirus and the Ras protein expression in LSCC xenograft tumours was also downregulate by ASO-miR-21. Taken together, our data suggest that miR-21 may play an oncogenic role in the cellular processes of LSCC and represent a novel target for effective therapies.

摘要

miRNAs 是小的、非编码 RNA 分子,作为癌症相关过程的重要调节剂出现。miR-21 微 RNA 在多种癌症中过度表达,并与细胞增殖和凋亡有关。在这项研究中,我们发现 miR-21 在喉鳞状细胞癌 (LSCC) 中过度表达,并与晚期相关。反义寡核苷酸 (ASO) 抑制 miR-21 导致 Ras 蛋白水平降低,并显著抑制细胞增殖和侵袭。暴露于 miR-21 ASO 的 Hep-2 细胞在 G1 期停滞并增加凋亡。此外,重复注射 ASO-miR-21 慢病毒显著抑制 LSCC 异种移植瘤的生长,ASO-miR-21 还下调 LSCC 异种移植瘤中的 Ras 蛋白表达。总之,我们的数据表明,miR-21 可能在 LSCC 的细胞过程中发挥致癌作用,并代表有效治疗的新靶标。

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