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RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R
BACKGROUND: Non‐small cell lung cancer (NSCLC) is one of the most malignant cancer types, characterized by a poor prognosis. N6‐methyladenosine (m6A) is a prevalent internal modification of mRNA. METTL14, an RNA methyltransferase that mediates m6A modification, is implicated in mRNA biogenesis. Howe...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons Australia, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870747/ https://www.ncbi.nlm.nih.gov/pubmed/36448247 http://dx.doi.org/10.1111/1759-7714.14741 |
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author | Ren, Siying Xiao, Ying Yang, Lulu Hu, Yan |
author_facet | Ren, Siying Xiao, Ying Yang, Lulu Hu, Yan |
author_sort | Ren, Siying |
collection | PubMed |
description | BACKGROUND: Non‐small cell lung cancer (NSCLC) is one of the most malignant cancer types, characterized by a poor prognosis. N6‐methyladenosine (m6A) is a prevalent internal modification of mRNA. METTL14, an RNA methyltransferase that mediates m6A modification, is implicated in mRNA biogenesis. However, the biomechanism of METTL14 in NSCLC is not very clear. METHODS: Here, immunohistochemical (IHC) assay was employed to detect METTL14 in NSCLC tissues. The biological functions of METTL14 were demonstrated using cell transfection, cell proliferation assay, cell clone formation assay, cell cycle analysis, cell death analysis, transwell and wound healing assays. Transcriptome and methylated RNA immunoprecipitation (MERIP)‐sequencing were used to explore the pathways and potential mechanism of METTL14 in NSCLC. RNA sequencing, METTL14 rip‐sequencing, and METTL14 merip‐sequencing were conducted to identify the potential targets of METTL14. RESULTS: METTL14 was significantly correlated with clinical pathological parameters of differentiation and M stage. Additionally, METTL14 promotes cell proliferation, induces cell death, and enhances cell migration and invasion in vitro. Transcriptome and MeRIP‐sequencing reveal oncogenic mechanism of METTL14. RIP‐sequencing highlights CSF1R and AKR1C1 as targets of METTL14. After validation with TCGA dataset, colony stimulating factor 1 receptor (CSF1R) showed significant positive coefficient with METTL14, and was presumed to be one target of METTl14 in lung cancer and verified by the cellular experiments. CONCLUSION: In conclusion, our results revealed the clinical significance of m6A RNA modification atlas, the function, and molecular targets CSF1R of METTL14 in NSCLC cell lines. The RNA m6A methyltransferase METTL14 promotes the progression of NSCLC by targeted CSF1R. |
format | Online Article Text |
id | pubmed-9870747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons Australia, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-98707472023-01-25 RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R Ren, Siying Xiao, Ying Yang, Lulu Hu, Yan Thorac Cancer Original Articles BACKGROUND: Non‐small cell lung cancer (NSCLC) is one of the most malignant cancer types, characterized by a poor prognosis. N6‐methyladenosine (m6A) is a prevalent internal modification of mRNA. METTL14, an RNA methyltransferase that mediates m6A modification, is implicated in mRNA biogenesis. However, the biomechanism of METTL14 in NSCLC is not very clear. METHODS: Here, immunohistochemical (IHC) assay was employed to detect METTL14 in NSCLC tissues. The biological functions of METTL14 were demonstrated using cell transfection, cell proliferation assay, cell clone formation assay, cell cycle analysis, cell death analysis, transwell and wound healing assays. Transcriptome and methylated RNA immunoprecipitation (MERIP)‐sequencing were used to explore the pathways and potential mechanism of METTL14 in NSCLC. RNA sequencing, METTL14 rip‐sequencing, and METTL14 merip‐sequencing were conducted to identify the potential targets of METTL14. RESULTS: METTL14 was significantly correlated with clinical pathological parameters of differentiation and M stage. Additionally, METTL14 promotes cell proliferation, induces cell death, and enhances cell migration and invasion in vitro. Transcriptome and MeRIP‐sequencing reveal oncogenic mechanism of METTL14. RIP‐sequencing highlights CSF1R and AKR1C1 as targets of METTL14. After validation with TCGA dataset, colony stimulating factor 1 receptor (CSF1R) showed significant positive coefficient with METTL14, and was presumed to be one target of METTl14 in lung cancer and verified by the cellular experiments. CONCLUSION: In conclusion, our results revealed the clinical significance of m6A RNA modification atlas, the function, and molecular targets CSF1R of METTL14 in NSCLC cell lines. The RNA m6A methyltransferase METTL14 promotes the progression of NSCLC by targeted CSF1R. John Wiley & Sons Australia, Ltd 2022-11-29 /pmc/articles/PMC9870747/ /pubmed/36448247 http://dx.doi.org/10.1111/1759-7714.14741 Text en © 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Ren, Siying Xiao, Ying Yang, Lulu Hu, Yan RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R |
title |
RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R
|
title_full |
RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R
|
title_fullStr |
RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R
|
title_full_unstemmed |
RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R
|
title_short |
RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R
|
title_sort | rna m6a methyltransferase mettl14 promotes the procession of non‐small cell lung cancer by targeted csf1r |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870747/ https://www.ncbi.nlm.nih.gov/pubmed/36448247 http://dx.doi.org/10.1111/1759-7714.14741 |
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