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Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway

BACKGROUND: Gastric cancer (GC) is a malignancy with high morbidity and mortality rates worldwide. SNHG12 is a long noncoding RNA (lncRNA) commonly involved many types of cancers in the contexts of tumorigenesis, migration and drug resistance. Nevertheless, its role in GC proliferation is poorly und...

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Autores principales: Zhang, Tianqi, Beeharry, Maneesh Kumarsing, Zheng, Yanan, Wang, Zhenqiang, Li, Jianfang, Zhu, Zhenggang, Li, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236831/
https://www.ncbi.nlm.nih.gov/pubmed/34195070
http://dx.doi.org/10.3389/fonc.2021.645832
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author Zhang, Tianqi
Beeharry, Maneesh Kumarsing
Zheng, Yanan
Wang, Zhenqiang
Li, Jianfang
Zhu, Zhenggang
Li, Chen
author_facet Zhang, Tianqi
Beeharry, Maneesh Kumarsing
Zheng, Yanan
Wang, Zhenqiang
Li, Jianfang
Zhu, Zhenggang
Li, Chen
author_sort Zhang, Tianqi
collection PubMed
description BACKGROUND: Gastric cancer (GC) is a malignancy with high morbidity and mortality rates worldwide. SNHG12 is a long noncoding RNA (lncRNA) commonly involved many types of cancers in the contexts of tumorigenesis, migration and drug resistance. Nevertheless, its role in GC proliferation is poorly understood. METHODS: Bioinformatics and qRT-PCR assays were used to analyze the expression of SNHG12 in GC tissues and cells. In vitro and in vivo experiments were conducted to detect the role of SNHG12 in GC development. qRT-PCR, PCR, western blotting (WB), RNA binding protein immunoprecipitation (RIP), immunoprecipitation (IP), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) were performed to investigate the underlying mechanisms by which SNHG12 promotes GC proliferation. RESULTS: SNHG12 was highly expressed in GC cells and tissues, and predicted poor survival. In vitro and in vivo assays showed that SNHG12 knockdown inhibited GC proliferation, while SNHG12 overexpression promoted GC proliferation. Further experiments confirmed that SNHG12 was mainly located in the cytoplasm and bound to HuR. Bioinformatics analysis predicted that YWHAZ was the common target of SNHG12 and HuR, and that the “SNHG12-HuR” complex enhanced the stability of YWHAZ mRNA. Furthermore, YWHAZ, which was highly expressed in GC, predicted poor survival and promoted GC proliferation by phosphorylating AKT. Rescue assays verified that SNHG12 promoted GC proliferation by activating the AKT/GSK-3β pathway. CONCLUSIONS: SNHG12 binds to HuR and stabilizes YWHAZ. SNHG12 promotes GC proliferation via modulation of the YWHAZ/AKT/GSK-3β axis in vitro and in vivo. Thus, SNHG12 could become a novel therapeutic target for anti-tumor therapy.
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spelling pubmed-82368312021-06-29 Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway Zhang, Tianqi Beeharry, Maneesh Kumarsing Zheng, Yanan Wang, Zhenqiang Li, Jianfang Zhu, Zhenggang Li, Chen Front Oncol Oncology BACKGROUND: Gastric cancer (GC) is a malignancy with high morbidity and mortality rates worldwide. SNHG12 is a long noncoding RNA (lncRNA) commonly involved many types of cancers in the contexts of tumorigenesis, migration and drug resistance. Nevertheless, its role in GC proliferation is poorly understood. METHODS: Bioinformatics and qRT-PCR assays were used to analyze the expression of SNHG12 in GC tissues and cells. In vitro and in vivo experiments were conducted to detect the role of SNHG12 in GC development. qRT-PCR, PCR, western blotting (WB), RNA binding protein immunoprecipitation (RIP), immunoprecipitation (IP), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) were performed to investigate the underlying mechanisms by which SNHG12 promotes GC proliferation. RESULTS: SNHG12 was highly expressed in GC cells and tissues, and predicted poor survival. In vitro and in vivo assays showed that SNHG12 knockdown inhibited GC proliferation, while SNHG12 overexpression promoted GC proliferation. Further experiments confirmed that SNHG12 was mainly located in the cytoplasm and bound to HuR. Bioinformatics analysis predicted that YWHAZ was the common target of SNHG12 and HuR, and that the “SNHG12-HuR” complex enhanced the stability of YWHAZ mRNA. Furthermore, YWHAZ, which was highly expressed in GC, predicted poor survival and promoted GC proliferation by phosphorylating AKT. Rescue assays verified that SNHG12 promoted GC proliferation by activating the AKT/GSK-3β pathway. CONCLUSIONS: SNHG12 binds to HuR and stabilizes YWHAZ. SNHG12 promotes GC proliferation via modulation of the YWHAZ/AKT/GSK-3β axis in vitro and in vivo. Thus, SNHG12 could become a novel therapeutic target for anti-tumor therapy. Frontiers Media S.A. 2021-06-14 /pmc/articles/PMC8236831/ /pubmed/34195070 http://dx.doi.org/10.3389/fonc.2021.645832 Text en Copyright © 2021 Zhang, Beeharry, Zheng, Wang, Li, Zhu and Li 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
Zhang, Tianqi
Beeharry, Maneesh Kumarsing
Zheng, Yanan
Wang, Zhenqiang
Li, Jianfang
Zhu, Zhenggang
Li, Chen
Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
title Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
title_full Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
title_fullStr Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
title_full_unstemmed Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
title_short Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
title_sort long noncoding rna snhg12 promotes gastric cancer proliferation by binding to hur and stabilizing ywhaz expression through the akt/gsk-3β pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236831/
https://www.ncbi.nlm.nih.gov/pubmed/34195070
http://dx.doi.org/10.3389/fonc.2021.645832
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