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METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis

OBJECTIVES: METTL3 as an m(6)A methyltransferase acts in diverse malignancies including gastric cancer (GC). We aimed to reveal the underlying mechanisms by which METTL3 contributes to gastric carcinogenesis. METHODS: The association of METTL3 and SNHG3 with GC was analyzed by qRT-PCR, Western blot,...

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Autores principales: Ji, Guo, Wang, Xiu, Xi, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571673/
https://www.ncbi.nlm.nih.gov/pubmed/37823387
http://dx.doi.org/10.1177/03946320231204694
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author Ji, Guo
Wang, Xiu
Xi, Hao
author_facet Ji, Guo
Wang, Xiu
Xi, Hao
author_sort Ji, Guo
collection PubMed
description OBJECTIVES: METTL3 as an m(6)A methyltransferase acts in diverse malignancies including gastric cancer (GC). We aimed to reveal the underlying mechanisms by which METTL3 contributes to gastric carcinogenesis. METHODS: The association of METTL3 and SNHG3 with GC was analyzed by qRT-PCR, Western blot, and TCGA cohort. The functional experiments were implemented to uncover the role of METTL3 in GC. m(6)A dot blot and MeRIP were used to determine METTL3-mediated m(6)A modification of lncRNA SNHG3. The effect of METTL3 on SNHG3-mediated miR-186-5p/cyclinD2 axis was evaluated by luciferase gene report, RT-qPCR, and Western blot assays. RESULTS: We found that METTL3 was remarkably elevated in GC tissues and correlated with poor survival in patients with GC. Silencing of METTL3 impaired GC cell growth and invasion, whereas restored METTL3 expression promoted these effects. Mechanistically, reduced expression of METTL3 decreased SNHG3 m(6)A level and caused a decrease in SNHG3 expression, which could further act as a sponge of miR-186-5p to upregulate cyclinD2. Overexpression of SNHG3 attenuated METTL3 knockdown-induced anti-proliferating and miR-186-5p upregulation and cyclinD2 downregulation. CONCLUSION: We find that METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates GC progression by modulating miR-186-5p/cyclinD2 axis.
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spelling pubmed-105716732023-10-14 METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis Ji, Guo Wang, Xiu Xi, Hao Int J Immunopathol Pharmacol Original Research Article OBJECTIVES: METTL3 as an m(6)A methyltransferase acts in diverse malignancies including gastric cancer (GC). We aimed to reveal the underlying mechanisms by which METTL3 contributes to gastric carcinogenesis. METHODS: The association of METTL3 and SNHG3 with GC was analyzed by qRT-PCR, Western blot, and TCGA cohort. The functional experiments were implemented to uncover the role of METTL3 in GC. m(6)A dot blot and MeRIP were used to determine METTL3-mediated m(6)A modification of lncRNA SNHG3. The effect of METTL3 on SNHG3-mediated miR-186-5p/cyclinD2 axis was evaluated by luciferase gene report, RT-qPCR, and Western blot assays. RESULTS: We found that METTL3 was remarkably elevated in GC tissues and correlated with poor survival in patients with GC. Silencing of METTL3 impaired GC cell growth and invasion, whereas restored METTL3 expression promoted these effects. Mechanistically, reduced expression of METTL3 decreased SNHG3 m(6)A level and caused a decrease in SNHG3 expression, which could further act as a sponge of miR-186-5p to upregulate cyclinD2. Overexpression of SNHG3 attenuated METTL3 knockdown-induced anti-proliferating and miR-186-5p upregulation and cyclinD2 downregulation. CONCLUSION: We find that METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates GC progression by modulating miR-186-5p/cyclinD2 axis. SAGE Publications 2023-10-12 /pmc/articles/PMC10571673/ /pubmed/37823387 http://dx.doi.org/10.1177/03946320231204694 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Article
Ji, Guo
Wang, Xiu
Xi, Hao
METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis
title METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis
title_full METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis
title_fullStr METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis
title_full_unstemmed METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis
title_short METTL3-mediated m(6)A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis
title_sort mettl3-mediated m(6)a modification of lncrna snhg3 accelerates gastric cancer progression by modulating mir-186-5p/cyclind2 axis
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571673/
https://www.ncbi.nlm.nih.gov/pubmed/37823387
http://dx.doi.org/10.1177/03946320231204694
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