Long non‑coding RNA NNT‑AS1 knockdown represses the progression of gastric cancer via modulating the miR‑142‑5p/SOX4/Wnt/β‑catenin signaling pathway

Zhang,Jianfeng; Zhang,Kai; Hou,Yingkui

doi:10.3892/mmr.2020.11158

Long non‑coding RNA NNT‑AS1 knockdown represses the progression of gastric cancer via modulating the miR‑142‑5p/SOX4/Wnt/β‑catenin signaling pathway

Authors:
- Jianfeng Zhang
- Kai Zhang
- Yingkui Hou
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Affiliations: Department of Gastrointestinal Surgery, The First People's Hospital of Guangyuan, Guangyuan, Sichuan 628017, P.R. China
Published online on: May 18, 2020 https://doi.org/10.3892/mmr.2020.11158
Pages: 687-696
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Patients with advanced gastric cancer (GC) have a poor prognosis with a median overall survival of 10‑12 months. Long non‑coding RNA nicotinamide nucleotide transhydrogenase‑antisense RNA1 (NNT‑AS1) and sex‑determining region Y‑related high mobility group box 4 (SOX4) have been reported to be associated with the progression of various types of cancer; however, the regulatory mechanism between NNT‑AS1 and SOX4 in GC is not completely understood. Reverse transcription‑quantitative PCR was used to detect the expression levels of NNT‑AS1, microRNA (miR)‑142‑5p and SOX4. Western blotting was performed to assess the protein expression levels of SOX4, β‑catenin, c‑Myc, Bcl‑2 and E‑cadherin. The proliferation, apoptosis, migration and invasion of GC cells were determined using MTT, flow cytometry and Transwell assays. The relationship between miR‑142‑5p and NNT‑AS1 or SOX4 was investigated using a dual‑luciferase reporter assay. NNT‑AS1 and SOX4 were upregulated, whereas miR‑142‑5p was downregulated in GC tissues and cells compared with normal tissues and cells. Both NNT‑AS1 and SOX4 knockdown inhibited GC cell proliferation, migration and invasion, and enhanced GC cell apoptosis. Moreover, the results indicated that NNT‑AS1 modulated SOX4 expression by sponging miR‑142‑5p. In addition, SOX4 overexpression reversed NNT‑AS1 knockdown‑mediated effects on GC cell proliferation, apoptosis, migration and invasion. NNT‑AS1 knockdown blocked the Wnt/β‑catenin signaling pathway via the miR‑142‑5p/SOX4 axis. Collectively, the present study indicated that NNT‑AS1 knockdown decreased GC cell proliferation, migration and invasion, and induced GC cell apoptosis by regulating the miR‑142‑5p/SOX4/Wnt/β‑catenin signaling pathway axis.

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