Long Noncoding RNA Nuclear Paraspeckle Assembly Transcript 1 Promotes Progression and Angiogenesis of Esophageal Squamous Cell Carcinoma Through miR-590-3p/MDM2 Axis

Jing Luo,Kai Xie,Liwen Hu,Binhui Ren,Yang Xu,Xiaokun Li,Gaoming Wang,Yi Shen,Yu Yao,Xiang Gao,Chenye Shao

doi:10.3389/fonc.2020.618930

Abstract

Angiogenesis has been identified as one of the hallmarks of cancer and aggravates cancer development and progression. Accumulating evidence indicated that long noncoding RNAs (lncRNAs) are powerful factors in regulating various cancer behaviors. The aim of this study is to verify the function and potential mechanisms of lncRNA NEAT1 in progression and angiogenesis of esophageal squamous cell carcinoma (ESCC). We found that NEAT1 was overexpressed in ESCC tissues and correlated with clinical characteristics of patients. Silence of NEAT1 inhibited proliferation, migration, invasion and angiogenesis of ESCC cells. High throughput sequencing and western blotting revealed that NEAT1 regulated MDM2/p53 pathway. Rescue of MDM2 restored the effect of NEAT1 on progression and angiogenesis of ESCC cells. Nude mice xenograft models further validated the role of NEAT1 in vivo. Importantly, NEAT1 functioned as a competing endogenous RNA for miR-590-3p to regulate MDM2 expression and miR-590-3p acted as a tumor suppressor in ESCC progression and angiogenesis. These findings suggested that NEAT1/miR-590-3p/MDM2 axis might serve as potential therapeutic targets for ESCC patients.

Highlights

Esophageal cancer is one of the most predominant malignancies and ranks sixth in terms of cancer-related death worldwide [1]
QRT-PCR was performed to verify the expression of Nuclear paraspeckle assembly transcript 1 (NEAT1) in 80 paired esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues, and we found that NEAT1 was significantly up-regulated in ESCC tissues (Figure 1A)
As miR-590-3p was a sponge for NEAT1 and regulated its expression, we furtherly investigated the role of miR-590-3p on cancer progression and angiogenesis in ESCC

Summary

Introduction

Esophageal cancer is one of the most predominant malignancies and ranks sixth in terms of cancer-related death worldwide [1]. As the most predominant histological subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC) accounts for about 90% of all the esophageal cancer cases [2]. It is necessary to explore the molecular and pathogenic mechanisms of ESCC in-depth to develop novel ESCC anticancer agents. Angiogenesis has been identified as the novel hallmark of cancer and is essential for sustaining the development of tumor growth and metastasis [5]. The pathological angiogenesis in cancer is driven by an imbalance between pro-angiogenic and anti-angiogenic factors, which leads to replenishment of a new vessel supply [6]. Tumor angiogenesis is regarded as a key target for cancer therapy and anti-angiogenic agents exhibit effective inhibition on tumor progression and metastasis [7]. Further research of vital molecules in the regulation of angiogenesis of ESCC might provide potential target for ESCC therapy

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