LncRNA NEAT1 Regulates Cell Viability and Invasion in Esophageal Squamous Cell Carcinoma through the miR-129/CTBP2 Axis.

Yong Li,Gongning Shi,Xiang Gao,Dong Chen,Xiaohui Li

doi:10.1155/2017/5314649

Abstract

Background Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be aberrantly upregulated and promote esophageal squamous cell carcinoma (ESCC) cell progression. Nevertheless, the molecular mechanism of NEAT1 involved in the competing endogenous RNA (ceRNA) regulatory network in ESCC progression remains poorly defined. Methods The expressions of NEAT1, miR-129, and C-terminal-binding protein 2 (CTBP2) in ESCC cells were examined by qRT-PCR. The effects of NEAT1 knockdown and miR-129 overexpression, or along with CTBP2 upregulation, on ESCC cell viability and invasion were explored by CCK-8 and transwell invasion assays, respectively. Luciferase reporter assay in combination with RIP was performed to confirm the interaction between NEAT1, miR-129, and CTBP2. Results NEAT1 and CTBP2 were upregulated and miR-129 was downregulated in ESCC cells. Either NEAT1 knockdown or miR-129 overexpression suppressed ESCC cell viability and invasion. Moreover, NEAT1 functioned as an endogenous sponge to downregulate miR-129 by competitively binding to miR-129, thereby leading to the derepression of CTBP2, a target of miR-129. CTBP2 restoration overturned cell viability and invasion suppression mediated by NEAT1 knockdown or miR-129 overexpression. Conclusion LncRNA NEAT1 regulated ESCC cell viability and invasion via the miR-129/CTBP2 axis, contributing to the better understanding of the molecular mechanism of ESCC pathogenesis and progression.

Highlights

Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer (EC) and is considered one of the most common and leading aggressive malignancies all around the world, with an unexpectedly high fatality rate [1]
Cell Counting Kit-8 (CCK-8) results showed that cell viability was effectively inhibited in EC109 and EC9706 cells transfected with si-nuclear paraspeckle assembly transcript 1 (NEAT1) (Figures 2(b) and 2(d)) or miR129 mimic (Figures 2(g) and 2(i)) compared with si-control or miR-control groups
Our study provided an insight into the molecular mechanism of NEAT1 in esophageal squamous cell carcinoma (ESCC) progression and identified that the dysregulation of the NEAT1/miR-129/C-terminal-binding protein 2 (CTBP2) axis accounted for ESCC progression

Summary

Introduction

Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer (EC) and is considered one of the most common and leading aggressive malignancies all around the world, with an unexpectedly high fatality rate [1]. LncRNA HOTTIP was reported to be upregulated in ESCC, and knockdown of HOTTIP significantly inhibited ESCC cell proliferation and invasion [12]. LncRNA CASC9 was found to be markedly elevated in ESCC tissues, and downregulation of CASC9 suppressed ESCC cell migration and invasion [13]. NEAT1 was reported to be aberrantly upregulated and promote ESCC progression by stimulating cell proliferation and enhancing cells’ ability of forming foci, migration, and invasion [20]. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be aberrantly upregulated and promote esophageal squamous cell carcinoma (ESCC) cell progression. CTBP2 restoration overturned cell viability and invasion suppression mediated by NEAT1 knockdown or miR-129 overexpression. LncRNA NEAT1 regulated ESCC cell viability and invasion via the miR-129/CTBP2 axis, contributing to the better understanding of the molecular mechanism of ESCC pathogenesis and progression

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Discussion

Conclusion