ZEB1-induced LINC01559 expedites cell proliferation, migration and EMT process in gastric cancer through recruiting IGF2BP2 to stabilize ZEB1 expression

Huojian Shen,Weiqing Qiu,Yuanwen Chen,Changlin Qian,Hongyi Zhu,Jie Zhang,Zhiyong Shen

doi:10.1038/s41419-021-03571-5

Huojian Shen, Weiqing Qiu + Show 5 more

Open Access

https://doi.org/10.1038/s41419-021-03571-5

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Journal: Cell Death & Disease	Publication Date: Apr 1, 2021
Citations: 33	License type: open-access

Affiliation: Renji Hospital, Shanghai Jiao Tong University

Abstract

Gastric cancer (GC) is a common type of tumor that is characterized with high metastatic rate. In recent years, increasing studies have indicated that lncRNAs are involved in the regulation on cancer cell proliferation and migration. However, the functional role of long intergenic non-protein coding RNA 1559 (LINC01559) in GC is still unclear. In this study, we applied quantitative real-time polymerase chain reaction (RT-qPCR) and examined that LINC01559 expression was significantly enhanced in GC cells. Functional assays such as EdU, colony formation, JC-1 and transwell assays displayed that silencing LINC01559 inhibited cell proliferation and migration while promoted cell apoptosis in GC. Besides, western blot analysis and immunofluorescence assays examined the expression of factors related to epithelial-mesenchymal transition (EMT) and indicated that EMT process was blocked by LINC01559 knockdown in GC cells. Besides, LINC01559 silencing inhibited tumor growth in vivo. In addition, Chromatin immunoprecipitation (ChIP) assays demonstrated that zinc finger E-box binding homeobox 1 (ZEB1) served as a transcription factor to combine with LINC01559 promoter and activated the expression of LINC01559 in GC cells. In return, LINC01559 recruited insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize ZEB1 mRNA to up-regulate ZEB1 in GC cells. In short, the findings in this research might provide a novel target for GC treatment.

Highlights

Nowadays, gastric cancer (GC) is one of the most common cancers worldwide[1]
We screened the data from GEPIA2 and found that LINC01559 expression was higher in 408 stomach adenocarcinoma
epithelialmesenchymal transition (EMT) is a biological process in which epithelialderived malignant cells transform into mesenchymal cells, and this process is related to cell migration and invasion[22]

Summary

Introduction

Gastric cancer (GC) is one of the most common cancers worldwide[1]. In East Asia, especially in Korea, Mongolia, Japan, and China, GC-associated morbidity and mortality have been shown to be relatively higher than in most western countries[2,3]. One of the main causes of cancer-related mortality is tumor. Long non-coding RNAs (lncRNAs) are a type of discovered RNAs with the length over 200 nucleotides and without the ability of coding proteins[6,7]. LncRNAs are involved in a wide range of biological processes in various cancers, such as cell proliferation, migration and apoptosis[8]. Expressed lncRNAs can serves as oncogenes or tumor suppressors to affect the progression and metastasis of cancers[9,10]. LncRNAs exert their functions majorly through the interaction with RNAs or proteins in the regulation of gene expression[11]. A large number of studies have shown that lncRNAs play vital roles in the progression of GC, such as MEG312, HOXA11-AS13 and LINC0033714.

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