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CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis

BACKGROUND: Gastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular...

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Autores principales: Gao, Ling, Xia, Tingting, Qin, Mingde, Xue, Xiaofeng, Jiang, Linhua, Zhu, Xinguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479173/
https://www.ncbi.nlm.nih.gov/pubmed/34604044
http://dx.doi.org/10.3389/fonc.2021.706415
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author Gao, Ling
Xia, Tingting
Qin, Mingde
Xue, Xiaofeng
Jiang, Linhua
Zhu, Xinguo
author_facet Gao, Ling
Xia, Tingting
Qin, Mingde
Xue, Xiaofeng
Jiang, Linhua
Zhu, Xinguo
author_sort Gao, Ling
collection PubMed
description BACKGROUND: Gastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown. METHODS: CircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK). RESULTS: The level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer. CONCLUSION: Collectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.
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spelling pubmed-84791732021-09-30 CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis Gao, Ling Xia, Tingting Qin, Mingde Xue, Xiaofeng Jiang, Linhua Zhu, Xinguo Front Oncol Oncology BACKGROUND: Gastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown. METHODS: CircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK). RESULTS: The level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer. CONCLUSION: Collectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer. Frontiers Media S.A. 2021-09-15 /pmc/articles/PMC8479173/ /pubmed/34604044 http://dx.doi.org/10.3389/fonc.2021.706415 Text en Copyright © 2021 Gao, Xia, Qin, Xue, Jiang and Zhu 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
Gao, Ling
Xia, Tingting
Qin, Mingde
Xue, Xiaofeng
Jiang, Linhua
Zhu, Xinguo
CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
title CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
title_full CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
title_fullStr CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
title_full_unstemmed CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
title_short CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
title_sort circptk2 suppresses the progression of gastric cancer by targeting the mir-196a-3p/aatk axis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479173/
https://www.ncbi.nlm.nih.gov/pubmed/34604044
http://dx.doi.org/10.3389/fonc.2021.706415
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