Wang Xinyu, Li Meng, Wang Zhiqiong, Han Sichong, Tang Xiaohu, Ge Yunxia, Zhou Liqing, Zhou Changchun, Yuan Qipeng, Yang Ming
From the State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian 223002, Jiangsu Province, China, and.
J Biol Chem. 2015 Feb 13;290(7):3925-35. doi: 10.1074/jbc.M114.596866. Epub 2014 Dec 23.
MALAT1, a highly conserved long noncoding RNA, is deregulated in several types of cancers. However, its role in esophageal squamous cell carcinoma (ESCC) and its posttranscriptional regulation remain poorly understood. In this study we provide first evidences that a posttranscriptional regulation mechanism of MALAT1 by miR-101 and miR-217 exists in ESCC cells. This posttranscriptional silencing of MALAT1 could significantly suppress the proliferation of ESCC cells through the arrest of G2/M cell cycle, which may be due to MALAT1-mediated up-regulation of p21 and p27 expression and the inhibition of B-MYB expression. Moreover, we also found the abilities of migration and invasion of ESCC cells were inhibited after overexpression of miR-101, miR-217, or MALAT1 siRNA. This might be attributed to the deregulation of downstream genes of MALAT1, such as MIA2, HNF4G, ROBO1, CCT4, and CTHRC1. A significant negative correlation exists between miR-101 or miR-217 and MALAT1 in 42 pairs of ESCC tissue samples and adjacent normal tissues. Mice xenograft data also support the tumor suppressor role of both miRNAs in ESCCs.
MALAT1是一种高度保守的长链非编码RNA，在多种癌症中表达失调。然而，其在食管鳞状细胞癌（ESCC）中的作用及其转录后调控仍知之甚少。在本研究中，我们首次提供证据表明，ESCC细胞中存在miR-101和miR-217对MALAT1的转录后调控机制。MALAT1的这种转录后沉默可通过使G2/M细胞周期停滞来显著抑制ESCC细胞的增殖，这可能是由于MALAT1介导的p21和p27表达上调以及B-MYB表达受到抑制。此外，我们还发现，过表达miR-101、miR-217或MALAT1 siRNA后，ESCC细胞的迁移和侵袭能力受到抑制。这可能归因于MALAT1下游基因（如MIA2、HNF4G、ROBO1、CCT4和CTHRC1）的失调。在42对ESCC组织样本及其相邻正常组织中，miR-101或miR-217与MALAT1之间存在显著的负相关。小鼠异种移植数据也支持这两种microRNA在ESCC中的肿瘤抑制作用。
