微小 RNA-362 通过激活 NF-κB 信号诱导胃癌细胞增殖和抗凋亡。

MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-κB signaling.

机构信息

Department of General Surgery, The third Affiliated Hospital, Guangzhou Medical University, #63 Duobao Road, Guangzhou, Guangdong 510150, China.

出版信息

J Transl Med. 2014 Feb 5;12:33. doi: 10.1186/1479-5876-12-33.

DOI:10.1186/1479-5876-12-33

PMID:24495516

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3916099/

Abstract

BACKGROUND

According to cancer-related microRNA (miRNA) expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer. However, the expression and biological role of miR-362 in gastric progression remain unclear.

METHODS

miR-362 expression levels in gastric cancer tissues and cell lines were determined using real-time PCR. The roles of miR-362, in promoting gastric cancer cell proliferation and apoptosis resistance, were assessed by different biological assays, such as colony assay, flow cytometry and TUNEL assay. The effect of miR-362 on NF-κB activation was investigated using the luciferase reporter assay, fluorescent immunostaining.

RESULTS

MiR-362 overexpression induced cell proliferation, colony formation, and resistance to cisplatin-induced apoptosis in BGC-823 and SGC-7901 gastric cancer cells. MiR-362 increased NF-κB activity and relative mRNA expression of NF-κB-regulated genes, and induced nuclear translocation of p65. Expression of the tumor suppressor CYLD was inhibited by miR-362 in gastric cancer cells; miR-362 levels were inversely correlated with CYLD expression in gastric cancer tissue. MiR-362 downregulated CYLD expression by binding its 3' untranslated region. NF-κB activation was mechanistically associated with siRNA-mediated downregulation of CYLD. MiR-362 inhibitor reversed all the effects of miR-362.

CONCLUSION

The results suggest that miR-362 plays an important role in repressing the tumor suppressor CYLD and present a novel mechanism of miRNA-mediated NF-κB activation in gastric cancer.

摘要

背景

根据公共数据库中可用的癌症相关 microRNA（miRNA）表达微阵列研究，miR-362 在胃癌中的表达上调。然而，miR-362 在胃癌进展中的表达和生物学作用尚不清楚。

方法

使用实时 PCR 测定胃癌组织和细胞系中 miR-362 的表达水平。通过不同的生物学测定，如集落形成实验、流式细胞术和 TUNEL 测定，评估 miR-362 促进胃癌细胞增殖和抗凋亡的作用。使用荧光免疫染色和荧光素酶报告基因测定研究 miR-362 对 NF-κB 激活的影响。

结果

miR-362 的过表达诱导 BGC-823 和 SGC-7901 胃癌细胞的细胞增殖、集落形成和对顺铂诱导的凋亡的抗性。miR-362 增加了 NF-κB 活性和 NF-κB 调节基因的相对 mRNA 表达，并诱导了 p65 的核转位。在胃癌细胞中，肿瘤抑制因子 CYLD 被 miR-362 抑制；miR-362 在胃癌组织中的水平与 CYLD 的表达呈负相关。miR-362 通过结合其 3'非翻译区下调 CYLD 的表达。NF-κB 的激活与 siRNA 介导的 CYLD 下调有关。miR-362 抑制剂逆转了 miR-362 的所有作用。