微小RNA-183通过靶向程序性细胞死亡蛋白4促进食管鳞状细胞癌的增殖和侵袭。
MicroRNA-183 promotes proliferation and invasion in oesophageal squamous cell carcinoma by targeting programmed cell death 4.
作者信息
Ren L-H, Chen W-X, Li S, He X-Y, Zhang Z-M, Li M, Cao R-S, Hao B, Zhang H-J, Qiu H-Q, Shi R-H
机构信息
1] Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, PR China [2] Department of Gastroenterology, Zhangjiagang First People's Hospital, Affiliated Hospital of Soochow University, Jiangsu Province, Suzhou 215006, PR China.
Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, PR China.
出版信息
Br J Cancer. 2014 Nov 11;111(10):2003-13. doi: 10.1038/bjc.2014.485. Epub 2014 Sep 11.
BACKGROUND
Dysregulated microRNAs (miRNAs) can serve as oncogenes or suppressors and are associated with many cancers, including oesophageal squamous cell carcinoma (ESCC).
METHODS
An alignment miRNA array was used to identify differentially expressed miRNAs in ESCC tissues. The expression of miR-183 and programmed cell death 4 (PDCD4) in oesophageal tissues from ESCC and early oesophageal carcinoma patients was examined by quantitative reverse transcriptase PCR and western blotting. A luciferase assay was performed to confirm miR-183 target genes. The effects of miR-183 on ESCC cells and the associated mechanisms were established by in vitro experiments.
RESULTS
We identified 51 upregulated miRNAs and 17 downregulated miRNAs in our array, and miR-183 was one of the most upregulated miRNAs. An inverse correlation between miR-183 and PDCD4 levels was found in ESCC tissues. Upregulated expression of miR-183 was not correlated with tumour stage or lymphatic metastasis in ESCC patients. The luciferase assay confirmed that miR-183 directly interacted with the PDCD4 mRNA 3'-untranslated region in ESCC cells. Overexpression of miR-183 led to decreased PDCD4 protein levels and promoted ESCC cell proliferation and invasion. Inhibition of the PI3K/Akt signalling pathway increased PDCD4 protein levels and decreased miR-183 expression in ESCC cells.
CONCLUSIONS
MiR-183 promotes ESCC cell proliferation and invasion by directly targeting PDCD4, which suggests that it is involved in the pathogenesis of ESCC.
背景
失调的微小RNA（miRNA）可作为癌基因或抑癌基因，与包括食管鳞状细胞癌（ESCC）在内的多种癌症相关。
方法
使用比对miRNA芯片鉴定ESCC组织中差异表达的miRNA。通过定量逆转录PCR和蛋白质印迹法检测ESCC患者及早期食管癌患者食管组织中miR-183和程序性细胞死亡4（PDCD4）的表达。进行荧光素酶报告基因检测以确认miR-183的靶基因。通过体外实验确定miR-183对ESCC细胞的作用及其相关机制。
结果
我们在芯片中鉴定出51个上调的miRNA和17个下调的miRNA，miR-183是上调最为显著的miRNA之一。在ESCC组织中发现miR-183与PDCD4水平呈负相关。miR-183的上调表达与ESCC患者的肿瘤分期或淋巴转移无关。荧光素酶报告基因检测证实miR-183在ESCC细胞中直接与PDCD4 mRNA的3'-非翻译区相互作用。miR-183的过表达导致PDCD4蛋白水平降低，并促进ESCC细胞增殖和侵袭。抑制PI3K/Akt信号通路可增加ESCC细胞中PDCD4蛋白水平并降低miR-183表达。
结论
MiR-183通过直接靶向PDCD4促进ESCC细胞增殖和侵袭，这表明它参与了ESCC的发病机制。
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