Long intergenic non-coding RNA 00152 promotes tumor cell cycle progression by binding to EZH2 and repressing p15 and p21 in gastric cancer.

Wen-Ming Chen,Rong Kong,Tong-Peng Xu,Ming-De Huang,Er-Bao Zhang,Rui Xia,Dao-Ping Sun,Yong-Qian Shu

doi:10.18632/oncotarget.6949

Wen-Ming Chen, Rong Kong + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.6949

Copy DOI

Abstract

Long noncoding RNAs (lncRNAs) play important regulatory roles in several human cancers. Integrated analysis revealed that expression of long intergenic non-coding RNA 152 (LINC00152) was significantly upregulated in gastric cancer (GC). Further analysis in a cohort of 97 GC patients revealed that LINC00152 expression was positively correlated with tumor invasion depth, lymph node metastasis, higher TNM stage, and poor survival. Gene set enrichment analysis revealed that cell proliferation and cell cycle progression were increased in patients with high LINC00152 expression. In both GC cell lines and xenograft systems, LINC00152 overexpression facilitated GC cell proliferation by accelerating the cell cycle, whereas LINC00152 knockdown had the opposite effect. Moreover, by binding to enhancer of zeste homolog 2 (EZH2), LINC00152 promotes GC tumor cell cycle progression by silencing the expression of p15 and p21. These findings suggest that LINC00152 may play contribute to the progression of GC and may be an effective therapeutic target.

Highlights

Seventy percent of all gastric cancer (GC) cases occur in developing countries, with half of all cases occurring in Eastern Asia alone [1]
By analyzing data (GSE13911) from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we identified 30 Long noncoding RNAs (lncRNAs) that were highly expressed in GC tissues as compared to normal gastric tissues (Supplementary Figure S1)
Aberrant lncRNA expression plays a key role in gastric carcinogenesis [25]

Summary

Introduction

Seventy percent of all gastric cancer (GC) cases occur in developing countries, with half of all cases occurring in Eastern Asia alone (predominantly China) [1]. In the early stages of GC, there are often no specific symptoms, and curative surgery is usually no longer an option at the time of diagnosis. Treatment options are limited due to the lack of knowledge of the molecular and genetic bases of gastric carcinogenesis [2]. A deeper understanding of the molecular mechanisms of GC will shed light on its pathogenesis, and identification of new biomarkers for diagnosis and prognosis may improve individualized treatment strategies in the future [2]. Numerous genetic and epigenetic alterations are associated with GC [3,4,5].

Methods

Results

Conclusion