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MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation
BACKGROUND: Ectopic expression of miRNAs promotes tumor development and progression. miRNA (miR)-320a is downregulated in many cancers, including gastric cancer (GC). However, the mechanism underlying its downregulation and the role of miR-320a in GC are unknown. AIM: To determine expression and bio...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815930/ https://www.ncbi.nlm.nih.gov/pubmed/31662823 http://dx.doi.org/10.4251/wjgo.v11.i10.842 |
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author | Li, Yong-Shuang Zou, Ying Dai, Dong-Qiu |
author_facet | Li, Yong-Shuang Zou, Ying Dai, Dong-Qiu |
author_sort | Li, Yong-Shuang |
collection | PubMed |
description | BACKGROUND: Ectopic expression of miRNAs promotes tumor development and progression. miRNA (miR)-320a is downregulated in many cancers, including gastric cancer (GC). However, the mechanism underlying its downregulation and the role of miR-320a in GC are unknown. AIM: To determine expression and biological functions of miR-320a in GC and investigate the underlying molecular mechanisms. METHODS: Quantitative real-time polymerase chain reaction (PCR) was used to determine expression of miR-320a in GC cell lines and tissues. TargetScanHuman7.1, miRDB, and microRNA.org were used to predict the possible targets of miR-320a, and a dual luciferase assay was used to confirm the findings. Western blotting was used to detect the protein levels of pre-B-cell leukemia homeobox 3 (PBX3) in GC cells and tissue samples. Cell Counting Kit-8 proliferation, Transwell, wound healing, and apoptosis assays were performed to analyze the biological functions of miR-320a in GC cells. Methylation-specific PCR was used to analyze the methylation level of the miR-320a promoter CpG islands. 5-Aza-2’-deoxycytidine (5-Aza-CdR) and trichostatin A (TSA) were used to treat GC cells. RESULTS: miR-320a expression was lower in GC cell lines and tissues than in the normal gastric mucosa cell line GES-1 and matched adjacent normal tissues. miR-320a overexpression suppressed GC cell proliferation, invasion and migration, and induced apoptosis. PBX3 was a target of miR-320a in GC. The methylation level of the miR-320a promoter CpG islands was elevated and this was partly reversed by 5-Aza-CdR and TSA. CONCLUSION: miR-320a acts as a tumor suppressor and inhibits malignant behavior of GC cells, partly by targeting PBX3. DNA methylation is an important mechanism associated with low expression of miR-320a. |
format | Online Article Text |
id | pubmed-6815930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-68159302019-10-29 MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation Li, Yong-Shuang Zou, Ying Dai, Dong-Qiu World J Gastrointest Oncol Basic Study BACKGROUND: Ectopic expression of miRNAs promotes tumor development and progression. miRNA (miR)-320a is downregulated in many cancers, including gastric cancer (GC). However, the mechanism underlying its downregulation and the role of miR-320a in GC are unknown. AIM: To determine expression and biological functions of miR-320a in GC and investigate the underlying molecular mechanisms. METHODS: Quantitative real-time polymerase chain reaction (PCR) was used to determine expression of miR-320a in GC cell lines and tissues. TargetScanHuman7.1, miRDB, and microRNA.org were used to predict the possible targets of miR-320a, and a dual luciferase assay was used to confirm the findings. Western blotting was used to detect the protein levels of pre-B-cell leukemia homeobox 3 (PBX3) in GC cells and tissue samples. Cell Counting Kit-8 proliferation, Transwell, wound healing, and apoptosis assays were performed to analyze the biological functions of miR-320a in GC cells. Methylation-specific PCR was used to analyze the methylation level of the miR-320a promoter CpG islands. 5-Aza-2’-deoxycytidine (5-Aza-CdR) and trichostatin A (TSA) were used to treat GC cells. RESULTS: miR-320a expression was lower in GC cell lines and tissues than in the normal gastric mucosa cell line GES-1 and matched adjacent normal tissues. miR-320a overexpression suppressed GC cell proliferation, invasion and migration, and induced apoptosis. PBX3 was a target of miR-320a in GC. The methylation level of the miR-320a promoter CpG islands was elevated and this was partly reversed by 5-Aza-CdR and TSA. CONCLUSION: miR-320a acts as a tumor suppressor and inhibits malignant behavior of GC cells, partly by targeting PBX3. DNA methylation is an important mechanism associated with low expression of miR-320a. Baishideng Publishing Group Inc 2019-10-15 2019-10-15 /pmc/articles/PMC6815930/ /pubmed/31662823 http://dx.doi.org/10.4251/wjgo.v11.i10.842 Text en ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Li, Yong-Shuang Zou, Ying Dai, Dong-Qiu MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation |
title | MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation |
title_full | MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation |
title_fullStr | MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation |
title_full_unstemmed | MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation |
title_short | MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation |
title_sort | microrna-320a suppresses tumor progression by targeting pbx3 in gastric cancer and is downregulated by dna methylation |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815930/ https://www.ncbi.nlm.nih.gov/pubmed/31662823 http://dx.doi.org/10.4251/wjgo.v11.i10.842 |
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