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MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer

MicroRNAs (miRNAs) are increasingly recognized as important therapeutic targets in cancer. Here we aim to investigate the role of miR-198, a broad-spectrum tumor suppressor, in gastric cancer (GC). MiR-198 overexpression was achieved by transfection of miR-198 mimics, followed by evaluation of cell...

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Detalles Bibliográficos
Autores principales: Gu, Junxia, Li, Xiaozhen, Li, Hui, Jin, Zhe, Jin, Jianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558723/
https://www.ncbi.nlm.nih.gov/pubmed/31138759
http://dx.doi.org/10.1042/BSR20181258
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author Gu, Junxia
Li, Xiaozhen
Li, Hui
Jin, Zhe
Jin, Jianjun
author_facet Gu, Junxia
Li, Xiaozhen
Li, Hui
Jin, Zhe
Jin, Jianjun
author_sort Gu, Junxia
collection PubMed
description MicroRNAs (miRNAs) are increasingly recognized as important therapeutic targets in cancer. Here we aim to investigate the role of miR-198, a broad-spectrum tumor suppressor, in gastric cancer (GC). MiR-198 overexpression was achieved by transfection of miR-198 mimics, followed by evaluation of cell viability using cell-counting kit 8. Cell cycle arrest and apoptosis were assessed by Annexin-V-FITC/Propidium Iodide (PI) staining flow cytometry respectively. The target of miR-198 was identified by bioinformatical analysis and confirmed by dual-luciferase assay, along with real-time PCR and Western blot analyses of target gene expression after transfection of miR-198 mimics. GC tissues were characterized by miR-198 down-regulation. Restoration of miR-198 expression attenuated GC cell proliferation and colony formation, meanwhile inducing significant G(0)/G(1) arrest. Furthermore, combinatory therapy of cisplatin and miR-198 induced greater anti-tumor effects than treatment with cisplatin single therapy. We also identified fibroblast growth factor receptor 1 (FGFR1) as a direct target gene of miR-198. Furthermore, FGFR1 silencing elicited a similar tumor-suppressive effect as miR-198 overexpression. FGFR1 overexpression antagonized the anti-tumor effects of miR-198 overexpression. MiR-198/FGFR1 axis plays an important role in proliferation and apoptosis of GC. Therapies targeted to miR-198 can potentially improve GC treatment.
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spelling pubmed-65587232019-06-20 MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer Gu, Junxia Li, Xiaozhen Li, Hui Jin, Zhe Jin, Jianjun Biosci Rep Research Articles MicroRNAs (miRNAs) are increasingly recognized as important therapeutic targets in cancer. Here we aim to investigate the role of miR-198, a broad-spectrum tumor suppressor, in gastric cancer (GC). MiR-198 overexpression was achieved by transfection of miR-198 mimics, followed by evaluation of cell viability using cell-counting kit 8. Cell cycle arrest and apoptosis were assessed by Annexin-V-FITC/Propidium Iodide (PI) staining flow cytometry respectively. The target of miR-198 was identified by bioinformatical analysis and confirmed by dual-luciferase assay, along with real-time PCR and Western blot analyses of target gene expression after transfection of miR-198 mimics. GC tissues were characterized by miR-198 down-regulation. Restoration of miR-198 expression attenuated GC cell proliferation and colony formation, meanwhile inducing significant G(0)/G(1) arrest. Furthermore, combinatory therapy of cisplatin and miR-198 induced greater anti-tumor effects than treatment with cisplatin single therapy. We also identified fibroblast growth factor receptor 1 (FGFR1) as a direct target gene of miR-198. Furthermore, FGFR1 silencing elicited a similar tumor-suppressive effect as miR-198 overexpression. FGFR1 overexpression antagonized the anti-tumor effects of miR-198 overexpression. MiR-198/FGFR1 axis plays an important role in proliferation and apoptosis of GC. Therapies targeted to miR-198 can potentially improve GC treatment. Portland Press Ltd. 2019-06-10 /pmc/articles/PMC6558723/ /pubmed/31138759 http://dx.doi.org/10.1042/BSR20181258 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
Gu, Junxia
Li, Xiaozhen
Li, Hui
Jin, Zhe
Jin, Jianjun
MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer
title MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer
title_full MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer
title_fullStr MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer
title_full_unstemmed MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer
title_short MicroRNA-198 inhibits proliferation and induces apoptosis by directly suppressing FGFR1 in gastric cancer
title_sort microrna-198 inhibits proliferation and induces apoptosis by directly suppressing fgfr1 in gastric cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558723/
https://www.ncbi.nlm.nih.gov/pubmed/31138759
http://dx.doi.org/10.1042/BSR20181258
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