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MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF

MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional a...

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Autores principales: Xu, Zhenglei, Yu, Zhichao, Tan, Qinghong, Wei, Cheng, Tang, Qi, Wang, Lisheng, Hong, Yingcai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597843/
https://www.ncbi.nlm.nih.gov/pubmed/31171711
http://dx.doi.org/10.1042/BSR20190066
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author Xu, Zhenglei
Yu, Zhichao
Tan, Qinghong
Wei, Cheng
Tang, Qi
Wang, Lisheng
Hong, Yingcai
author_facet Xu, Zhenglei
Yu, Zhichao
Tan, Qinghong
Wei, Cheng
Tang, Qi
Wang, Lisheng
Hong, Yingcai
author_sort Xu, Zhenglei
collection PubMed
description MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional and mechanistic impacts of a novel miRNA on GC cellular process. The significant down-regulation of miR-876-5p in GC cells attracted our attention. In function, we performed gain-of-function assays and found that miR-876-5p overexpression repressed proliferative, anti-apoptotic and migratory abilities and epithelial–mesenchymal transition (EMT) of GC cells. By applying bioinformatics prediction and mechanism experiments, we verified that miR-876-5p could double-bind to the 3′ untranslated regions (3′UTRs) of Wnt family member 5A (WNT5A) and melanogenesis associated transcription factor (MITF), thus regulating their mRNA and protein levels. Both WNT5A and MITF were highly expressed in GC cells. Additionally, we conducted loss-of-function assays and confirmed the oncogenic roles of WNT5A and MITF in GC. Finally, rescue assay uncovered a fact that miR-876-5p suppressed GC cell viability and migration, but induced cell apoptosis via targeting WNT5A and MITF. Taken together, we might offer a valuable evidence for miR-876-5p role in GC development.
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spelling pubmed-65978432019-07-05 MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF Xu, Zhenglei Yu, Zhichao Tan, Qinghong Wei, Cheng Tang, Qi Wang, Lisheng Hong, Yingcai Biosci Rep Research Articles MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional and mechanistic impacts of a novel miRNA on GC cellular process. The significant down-regulation of miR-876-5p in GC cells attracted our attention. In function, we performed gain-of-function assays and found that miR-876-5p overexpression repressed proliferative, anti-apoptotic and migratory abilities and epithelial–mesenchymal transition (EMT) of GC cells. By applying bioinformatics prediction and mechanism experiments, we verified that miR-876-5p could double-bind to the 3′ untranslated regions (3′UTRs) of Wnt family member 5A (WNT5A) and melanogenesis associated transcription factor (MITF), thus regulating their mRNA and protein levels. Both WNT5A and MITF were highly expressed in GC cells. Additionally, we conducted loss-of-function assays and confirmed the oncogenic roles of WNT5A and MITF in GC. Finally, rescue assay uncovered a fact that miR-876-5p suppressed GC cell viability and migration, but induced cell apoptosis via targeting WNT5A and MITF. Taken together, we might offer a valuable evidence for miR-876-5p role in GC development. Portland Press Ltd. 2019-06-28 /pmc/articles/PMC6597843/ /pubmed/31171711 http://dx.doi.org/10.1042/BSR20190066 Text en © 2019 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Xu, Zhenglei
Yu, Zhichao
Tan, Qinghong
Wei, Cheng
Tang, Qi
Wang, Lisheng
Hong, Yingcai
MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF
title MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF
title_full MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF
title_fullStr MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF
title_full_unstemmed MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF
title_short MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF
title_sort mir-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting wnt5a and mitf
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597843/
https://www.ncbi.nlm.nih.gov/pubmed/31171711
http://dx.doi.org/10.1042/BSR20190066
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