Yan Shuo, Jiang Haosheng, Fang Shiming, Yin Fang, Wang Zhenlei, Jia Yiping, Sun Xianjun, Wu Shaoqiu, Jiang Tinghui, Mao Aiwu
Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai,PR China.
Cell Physiol Biochem. 2015;37(1):375-86. doi: 10.1159/000430361. Epub 2015 Aug 27.
BACKGROUND/AIMS: Emerging evidence indicates that microRNA (miR)-340 is downregulated in various human cancers, suggesting that it acts as a tumor suppressor. The aim of the present study was to evaluate the expression and role of miR-340 in human esophageal squamous cell carcinoma (ESCC).
The expression of miR-340 was examined in 64 paired ESCC and adjacent non-tumor tissues by quantitative real time PCR. The effects of miR-340 on ESCC cell proliferation and metastasis were examined by MTT and Matrigel invasion assays. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Targets of miR-340 were identified by bioinformatics and verified by luciferase reporter assays, quantitative real-time PCR, and western blotting.
MiR-340 was significantly downregulated in ESCC tumor tissues compared to adjacent non-tumor tissues and in ESCC cell lines compared to esophageal endothelial cells. Overexpression of miR-340 inhibited ESCC cell growth, colony formation, and invasion, and tumor growth in a xenograft mouse model. PSAT1 was identified as a direct target of miR-340 and its ectopic expression partially reversed the miR-340 mediated inhibition of viability, invasion and EMT in ESCC cells. The expression of miR-340 was negatively correlated with that of PSAT1 in human ESCC samples.
MiR-340 functions as a tumor suppressor by modulating the expression of PSAT1 and may contribute to the progression and invasiveness of ESCC.
背景/目的：新出现的证据表明，微小RNA（miR）-340在多种人类癌症中表达下调，提示其具有肿瘤抑制作用。本研究旨在评估miR-340在人类食管鳞状细胞癌（ESCC）中的表达及作用。
采用定量实时PCR检测64对ESCC及其癌旁非肿瘤组织中miR-340的表达。通过MTT法和基质胶侵袭实验检测miR-340对ESCC细胞增殖和转移的影响。将细胞皮下接种到BALB/c裸鼠体内评估肿瘤生长情况。通过生物信息学方法鉴定miR-340的靶标，并通过荧光素酶报告基因实验、定量实时PCR和蛋白质印迹法进行验证。
与癌旁非肿瘤组织相比，ESCC肿瘤组织中miR-340表达显著下调；与食管内皮细胞相比，ESCC细胞系中miR-340表达也显著下调。miR-340过表达抑制了ESCC细胞生长、集落形成和侵袭，以及异种移植小鼠模型中的肿瘤生长。PSAT1被鉴定为miR-340的直接靶标，其异位表达部分逆转了miR-340介导的对ESCC细胞活力、侵袭和上皮-间质转化的抑制作用。在人类ESCC样本中，miR-340的表达与PSAT1的表达呈负相关。
miR-340通过调节PSAT1的表达发挥肿瘤抑制作用，可能参与了ESCC的进展和侵袭。
