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miR-424-5p 抑制胰腺癌中 SOCS6 的表达。

MicroRNA-424-5p suppresses the expression of SOCS6 in pancreatic cancer.

机构信息

Department of General Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, 410008, Changsha, Hunan Province, People's Republic of China.

出版信息

Pathol Oncol Res. 2013 Oct;19(4):739-48. doi: 10.1007/s12253-013-9637-x. Epub 2013 May 9.

Abstract

MicroRNAs (miRNAs) are a group of small non-coding RNA molecules predicted to control the activity of about 30 % of all protein-coding genes in mammals. The expression of microRNA-424-5p (miR-424-5p) has been shown to vary in multiple hematological and solid organ malignancies, such as pancreatic cancer. This study aimed to characterize the function of upregulated miR-424-5p in pancreatic cancer and show how downstream suppressor of cytokine-induced signaling 6 (SOCS6) is negatively regulated by miR-424-5p. MiR-424-5p and SOCS6 expression was detected using quantitative real-time PCR (qRT-PCR) in pancreatic cancer tissues and adjacent non-tumorous ductal epithelium tissues. Luciferase reporter assays were used to assess SOCS6 as a target of miR-424-5p. The downstream effect of SOCS6 was measured by qRT-PCR after miR-424-5p inhibition and SOCS6 upregulation. The functions of miR-424-5p in vitro in pancreatic cancer cells were measured by migration and invasion assays and flow cytometry. Results suggested miR-424-5p was significantly upregulated in pancreatic cancer and suppress the expression of SOCS6, and miR-424-5p increased proliferation, migration and invasion of pancreatic cancer cells, while inhibited cell apoptosis. It was concluded that miR-424-5p is frequently upregulated in pancreatic cancer and modulates ERK1/2 signaling pathway by negatively regulating SOCS6.

摘要

MicroRNAs (miRNAs) 是一组小的非编码 RNA 分子,据预测可以控制哺乳动物中约 30%的全部蛋白质编码基因的活性。miRNA-424-5p(miR-424-5p)的表达已在多种血液系统恶性肿瘤和实体器官恶性肿瘤中发生改变,例如胰腺癌。本研究旨在表征上调的 miR-424-5p 在胰腺癌中的功能,并展示下游细胞因子诱导的信号转导抑制因子 6(SOCS6)如何受到 miR-424-5p 的负调控。使用实时定量 PCR(qRT-PCR)检测胰腺癌组织和相邻非肿瘤性导管上皮组织中 miR-424-5p 和 SOCS6 的表达。使用荧光素酶报告基因检测评估 SOCS6 是否为 miR-424-5p 的靶标。抑制 miR-424-5p 并上调 SOCS6 后,通过 qRT-PCR 测量 SOCS6 的下游效应。通过迁移和侵袭测定以及流式细胞术测量 miR-424-5p 在体外对胰腺癌细胞的功能。结果表明,miR-424-5p 在胰腺癌中显著上调,抑制 SOCS6 的表达,miR-424-5p 增加胰腺癌细胞的增殖、迁移和侵袭,同时抑制细胞凋亡。结论是,miR-424-5p 在胰腺癌中经常上调,并通过负调控 SOCS6 来调节 ERK1/2 信号通路。

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