MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer
MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer
复制标题
DOI：
10.1016/j.yexcr.2009.06.001
复制
发表时间：
2009-09-10
影响因子：
3.7
通讯作者：
Lu, Pei-Jung
中科院分区：
文献类型：
--
作者：
Lee, Kuen-Haur;Goan, Yih-Gang;Lu, Pei-Jung
LATS 2是LATS肿瘤抑制基因家族的成员。它与细胞周期和细胞凋亡的调节有关。LATS 2基因杂合性丢失（洛）在食管癌中的发生频率较高。但LATS 2基因在食管癌中的表达及其调控机制尚不清楚。目前的研究表明，LATS 2蛋白表达在转录后水平上由miR-373介导，并且与食管癌细胞系中miR-373的量呈负相关。此外，我们证明了LATS 2蛋白的直接抑制是由miR-373介导的，并操纵miR-373的表达来影响食管癌细胞的生长。此外，这种相关性得到了离体收集的数据的支持，其中分析了来自食管鳞状细胞癌（ESCC）患者的食管癌组织。最后，通过miRNA微阵列分析，包括miR-373在内的四种miRNA在ESCC样品中过表达。我们的研究结果表明，miR-373可能是一个潜在的癌基因，它通过抑制LATS 2的表达参与了人食管癌的发生。(C)2009 Elsevier Inc. All rights reserved.
LATS2 is a member of the LATS tumor suppressor family. It has been implicated in regulation of the cell cycle and apoptosis. Frequent loss of heterozygosity (LOH) of LATS2 has been reported in human esophageal cancer. But, the LATS2 gene expression and its regulatory mechanism in esophageal cancer remain unclear. The present study has shown that LATS2 protein expression was mediated by miR-373 at the post-transcriptional level and inversely correlated with miR-373 amounts in esophageal cancer cell lines. Furthermore, we demonstrated that the direct inhibition of LATS2 protein was mediated by miR-373 and manipulated the expression of miR-373 to affect esophageal cancer cells growth. Moreover, this correlation was supported by data collected ex vivo, in which esophageal cancer tissues from esophageal squamous cell carcinoma (ESCC) patients were analyzed. Finally, by miRNA microarray analysis, four miRNAs including miR-373 were over-expressed in ESCC samples. Our findings reveal that miR-373 would be a potential oncogene and it participates in the carcinogenesis of human esophageal cancer by suppressing LATS2 expression. (C) 2009 Elsevier Inc. All rights reserved.