Cargando…
Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma
BACKGROUND: Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic marker...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393813/ https://www.ncbi.nlm.nih.gov/pubmed/34446007 http://dx.doi.org/10.1186/s12935-021-02163-9 |
_version_ | 1783743810633728000 |
---|---|
author | Liu, Jinfang Zhou, Zijian Ma, Ling Li, Chujun Lin, Yu Yu, Ting Wei, Ji-Fu Zhu, Lingjun Yao, Gang |
author_facet | Liu, Jinfang Zhou, Zijian Ma, Ling Li, Chujun Lin, Yu Yu, Ting Wei, Ji-Fu Zhu, Lingjun Yao, Gang |
author_sort | Liu, Jinfang |
collection | PubMed |
description | BACKGROUND: Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic markers and assess prognostic performance of N6-methyladenosine (m6A) regulators in melanoma. METHODS: Gene expression data and corresponding clinical informations of melanoma patients as well as sequence data of normal controls are collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Quantitative real-time PCR (qRT-PCR) analysis was carried out to detect the RNA expression of IGF2BP3 in A375 cell line, melanoma tissues, and normal tissues. Western blot, cell proliferation, and migration assays were performed to assess the ability of IGF2BP3 in A375 cell line. RESULTS: Differently expressed m6A regulators between tumor samples and normal samples were analyzed. A three-gene prognostic signature including IGF2BP3, RBM15B, and METTL16 was constructed, and the risk score of this signature was identified to be an independent prognostic indicator for melanoma. In addition, IGF2BP3 was verified to promote melanoma cell proliferation and migration in vitro and associate with lymph node metastasis in clinical samples. Moreover, risk score and the expression of IGF2BP3 were positively associated with the infiltrating immune cells and these hub genes made excellent potential drug targets in melanoma. CONCLUSION: We identified the genetic changes in m6A regulatory genes and constructed a three-gene risk signature with distinct prognostic value in melanoma. This research provided new insights into the epigenetic understanding of m6A regulators and novel therapeutic strategies in melanoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02163-9. |
format | Online Article Text |
id | pubmed-8393813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83938132021-08-30 Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma Liu, Jinfang Zhou, Zijian Ma, Ling Li, Chujun Lin, Yu Yu, Ting Wei, Ji-Fu Zhu, Lingjun Yao, Gang Cancer Cell Int Primary Research BACKGROUND: Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic markers and assess prognostic performance of N6-methyladenosine (m6A) regulators in melanoma. METHODS: Gene expression data and corresponding clinical informations of melanoma patients as well as sequence data of normal controls are collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Quantitative real-time PCR (qRT-PCR) analysis was carried out to detect the RNA expression of IGF2BP3 in A375 cell line, melanoma tissues, and normal tissues. Western blot, cell proliferation, and migration assays were performed to assess the ability of IGF2BP3 in A375 cell line. RESULTS: Differently expressed m6A regulators between tumor samples and normal samples were analyzed. A three-gene prognostic signature including IGF2BP3, RBM15B, and METTL16 was constructed, and the risk score of this signature was identified to be an independent prognostic indicator for melanoma. In addition, IGF2BP3 was verified to promote melanoma cell proliferation and migration in vitro and associate with lymph node metastasis in clinical samples. Moreover, risk score and the expression of IGF2BP3 were positively associated with the infiltrating immune cells and these hub genes made excellent potential drug targets in melanoma. CONCLUSION: We identified the genetic changes in m6A regulatory genes and constructed a three-gene risk signature with distinct prognostic value in melanoma. This research provided new insights into the epigenetic understanding of m6A regulators and novel therapeutic strategies in melanoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02163-9. BioMed Central 2021-08-26 /pmc/articles/PMC8393813/ /pubmed/34446007 http://dx.doi.org/10.1186/s12935-021-02163-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Liu, Jinfang Zhou, Zijian Ma, Ling Li, Chujun Lin, Yu Yu, Ting Wei, Ji-Fu Zhu, Lingjun Yao, Gang Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma |
title | Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma |
title_full | Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma |
title_fullStr | Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma |
title_full_unstemmed | Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma |
title_short | Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma |
title_sort | effects of rna methylation n6-methyladenosine regulators on malignant progression and prognosis of melanoma |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393813/ https://www.ncbi.nlm.nih.gov/pubmed/34446007 http://dx.doi.org/10.1186/s12935-021-02163-9 |
work_keys_str_mv | AT liujinfang effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT zhouzijian effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT maling effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT lichujun effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT linyu effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT yuting effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT weijifu effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT zhulingjun effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma AT yaogang effectsofrnamethylationn6methyladenosineregulatorsonmalignantprogressionandprognosisofmelanoma |