Department of General Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, 410008, Changsha, Hunan Province, People's Republic of China.
Pathol Oncol Res. 2013 Oct;19(4):739-48. doi: 10.1007/s12253-013-9637-x. Epub 2013 May 9.
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.
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。