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SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28

SNHG8, a family member of small nucleolar RNA host genes (SNHG), has been reported to act as an oncogene in gastric carcinoma (GC). However, its biological function in Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) remains unclear. This study investigated the role of SNHG8 in EBVaGC. Si...

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Autores principales: Zou, Changyan, Liao, Jinrong, Hu, Dan, Su, Ying, Lin, Huamei, Lin, Keyu, Luo, Xingguan, Zheng, Xiongwei, Zhang, Lurong, Huang, Tao, Lin, Xiandong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554152/
https://www.ncbi.nlm.nih.gov/pubmed/34722282
http://dx.doi.org/10.3389/fonc.2021.734694
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author Zou, Changyan
Liao, Jinrong
Hu, Dan
Su, Ying
Lin, Huamei
Lin, Keyu
Luo, Xingguan
Zheng, Xiongwei
Zhang, Lurong
Huang, Tao
Lin, Xiandong
author_facet Zou, Changyan
Liao, Jinrong
Hu, Dan
Su, Ying
Lin, Huamei
Lin, Keyu
Luo, Xingguan
Zheng, Xiongwei
Zhang, Lurong
Huang, Tao
Lin, Xiandong
author_sort Zou, Changyan
collection PubMed
description SNHG8, a family member of small nucleolar RNA host genes (SNHG), has been reported to act as an oncogene in gastric carcinoma (GC). However, its biological function in Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) remains unclear. This study investigated the role of SNHG8 in EBVaGC. Sixty-one cases of EBVaGC, 20 cases of non-EBV-infected gastric cancer (EBVnGC), and relative cell lines were studied for the expression of SNHG8 and BHRF1 (BCL2 homolog reading frame 1) encoded by EBV with Western blot and qRT-PCR assays. The relationship between the expression levels of SNHG8 and the clinical outcome in 61 EBVaGC cases was analyzed. Effects of overexpression or knockdown of BHRF1, SNHG8, or TRIM28 on cell proliferation, migration, invasion, and cell cycle and the related molecules were determined by several assays, including cell proliferation, colony assay, wound healing assay, transwell invasion assay, cell circle with flow cytometry, qRT-PCR, and Western blot for expression levels. The interactions among SNHG8, miR-512-5p, and TRIM28 were determined with Luciferase reporter assay, RNA immunoprecipitation (RIP), pull-down assays, and Western blot assay. The in vivo activity of SNHG8 was assessed with SNHG8 knockdown tumor xenografts in zebrafish. Results demonstrated that the following. (1) BHRF1 and SNHG8 were overexpressed in EBV-encoded RNA 1-positive EBVaGC tissues and cell lines. BHRF1 upregulated the expressions of SNHG8 and TRIM28 in AGS. (2) SNHG8 overexpression had a significant correlation with tumor size and vascular tumor thrombus. Patients with high SNHG8 expression had poorer overall survival (OS) compared to those with low SNHG8 expression. (3) SNHG8 overexpression promoted EBVaGC cell proliferation, migration, and invasion in vitro and in vivo, cell cycle arrested at the G2/M phase via the activation of BCL-2, CCND1, PCNA, PARP1, CDH1, CDH2 VIM, and Snail. (4) Results of dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assays indicated that SNHG8 sponged miR-512-5p, which targeted on TRIM28 and promoted cancer malignant behaviors of EBVaGC cells. Our data suggest that BHRF1 triggered the expression of SNHG8, which sponged miR-512-5p and upregulated TRIM28 and a set of effectors (such as BCL-2, CCND1, CDH1, CDH2 Snail, and VIM) to promote EBVaGC tumorigenesis and invasion. SNHG8 could be an independent prognostic factor for EBVaGC and sever as target for EBVaGC therapy.
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spelling pubmed-85541522021-10-30 SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28 Zou, Changyan Liao, Jinrong Hu, Dan Su, Ying Lin, Huamei Lin, Keyu Luo, Xingguan Zheng, Xiongwei Zhang, Lurong Huang, Tao Lin, Xiandong Front Oncol Oncology SNHG8, a family member of small nucleolar RNA host genes (SNHG), has been reported to act as an oncogene in gastric carcinoma (GC). However, its biological function in Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) remains unclear. This study investigated the role of SNHG8 in EBVaGC. Sixty-one cases of EBVaGC, 20 cases of non-EBV-infected gastric cancer (EBVnGC), and relative cell lines were studied for the expression of SNHG8 and BHRF1 (BCL2 homolog reading frame 1) encoded by EBV with Western blot and qRT-PCR assays. The relationship between the expression levels of SNHG8 and the clinical outcome in 61 EBVaGC cases was analyzed. Effects of overexpression or knockdown of BHRF1, SNHG8, or TRIM28 on cell proliferation, migration, invasion, and cell cycle and the related molecules were determined by several assays, including cell proliferation, colony assay, wound healing assay, transwell invasion assay, cell circle with flow cytometry, qRT-PCR, and Western blot for expression levels. The interactions among SNHG8, miR-512-5p, and TRIM28 were determined with Luciferase reporter assay, RNA immunoprecipitation (RIP), pull-down assays, and Western blot assay. The in vivo activity of SNHG8 was assessed with SNHG8 knockdown tumor xenografts in zebrafish. Results demonstrated that the following. (1) BHRF1 and SNHG8 were overexpressed in EBV-encoded RNA 1-positive EBVaGC tissues and cell lines. BHRF1 upregulated the expressions of SNHG8 and TRIM28 in AGS. (2) SNHG8 overexpression had a significant correlation with tumor size and vascular tumor thrombus. Patients with high SNHG8 expression had poorer overall survival (OS) compared to those with low SNHG8 expression. (3) SNHG8 overexpression promoted EBVaGC cell proliferation, migration, and invasion in vitro and in vivo, cell cycle arrested at the G2/M phase via the activation of BCL-2, CCND1, PCNA, PARP1, CDH1, CDH2 VIM, and Snail. (4) Results of dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assays indicated that SNHG8 sponged miR-512-5p, which targeted on TRIM28 and promoted cancer malignant behaviors of EBVaGC cells. Our data suggest that BHRF1 triggered the expression of SNHG8, which sponged miR-512-5p and upregulated TRIM28 and a set of effectors (such as BCL-2, CCND1, CDH1, CDH2 Snail, and VIM) to promote EBVaGC tumorigenesis and invasion. SNHG8 could be an independent prognostic factor for EBVaGC and sever as target for EBVaGC therapy. Frontiers Media S.A. 2021-10-15 /pmc/articles/PMC8554152/ /pubmed/34722282 http://dx.doi.org/10.3389/fonc.2021.734694 Text en Copyright © 2021 Zou, Liao, Hu, Su, Lin, Lin, Luo, Zheng, Zhang, Huang and Lin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zou, Changyan
Liao, Jinrong
Hu, Dan
Su, Ying
Lin, Huamei
Lin, Keyu
Luo, Xingguan
Zheng, Xiongwei
Zhang, Lurong
Huang, Tao
Lin, Xiandong
SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28
title SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28
title_full SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28
title_fullStr SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28
title_full_unstemmed SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28
title_short SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28
title_sort snhg8 promotes the progression of epstein–barr virus-associated gastric cancer via sponging mir-512-5p and targeting trim28
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554152/
https://www.ncbi.nlm.nih.gov/pubmed/34722282
http://dx.doi.org/10.3389/fonc.2021.734694
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