UCA1 promotes cell proliferation and invasion of gastric cancer by targeting CREB1 sponging to miR-590-3p.

Lei Gu,Zhong‐chen Liu,Dong‐lei Zhou,Lie‐sheng Lu

doi:10.1002/cam4.1310

Abstract

Long noncoding RNAs (lncRNAs) have emerged as regulators in a variety of biological processes, including carcinogenesis in human cancer. UCA1 has been reported to be upregulated in gastric cancer (GC); however, the underlying functional roles of UCA1 in GC have not been established. In the current study, we showed that UCA1 is significantly higher in GC tissues and cells compared with adjacent normal tissues and a gastric epithelium cell line, respectively. Higher UCA1 expression was associated with lymph node metastasis, TNM stage, and poor overall survival (OS) in GC patients. In vitro functional studies confirmed that UCA1 promotes cell proliferation, colony formation ability, and cell invasion in GC cells. We demonstrated that knockdown of UCA1 inhibits tumor growth in vivo. The double luciferase reporter, RNA‐binding protein immunoprecipitation assay, and RNA pull down assay demonstrated that miR‐590‐3p serves as a target for UCA1. UCA1 promoted cell proliferation and invasion by negatively regulating miR‐590‐3p expression. Moreover, we demonstrated that CREB1 is a downstream target of miR‐590‐3p and UCA1 activates CREB1 expression by sponging to miR‐590‐3p. Thus, these results showed that UCA1 functions as an oncogene in GC and may be a target for treatment of GC.

Highlights

Gastric cancer (GC) represents a large threat to public health with a high incidence and mortality rate worldwide
Upregulated long noncoding RNAs (lncRNAs)-urothelial carcinoma-associated 1 (UCA1) contributes to progression of lung cancer and is closely related to clinical diagnosis as a predictive biomarker in plasma [19]
We showed that UCA1 was higher in GC tissues and cells compared with adjacent normal tissues and GES-1 cell, respectively

Summary

Introduction

Gastric cancer (GC) represents a large threat to public health with a high incidence and mortality rate worldwide. Despite the large advances in diagnostic and therapeutic approaches, including surgical methods, radiotherapy, chemotherapy, and novel molecular targeted therapy for GC, the 5-year survival rate for patients who had been diagnosed in an advanced stage is poor [1, 2]. The molecular mechanisms underlying GC progression is in need of continued investigation to provide promising therapeutic targets. Accumulating evidence has highlighted that long noncoding RNAs (lncRNAs) play crucial roles in a variety of biological processes, including cell differentiation, proliferation, and apoptosis. Dysregulated expression of lncRNAs has been confirmed to be involved in GC development and progression [3, 4].

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Results

Conclusion