Cargando…
A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis
PURPOSE: Pancreatic adenocarcinoma (PAAD) remains a highly aggressive gastrointestinal malignancy with a dismal prognosis. Pyroptosis has a key role in tumor development. Long noncoding RNAs (lncRNAs) are involved in tumorigenesis and pyroptosis regulation. However, the prognostic potential and func...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618383/ https://www.ncbi.nlm.nih.gov/pubmed/37138146 http://dx.doi.org/10.1007/s13402-023-00818-5 |
_version_ | 1785129763738746880 |
---|---|
author | Li, Jingwei Lin, Jiewei Ji, Yuchen Wang, Xuelong Fu, Da Wang, Weishen Shen, Baiyong |
author_facet | Li, Jingwei Lin, Jiewei Ji, Yuchen Wang, Xuelong Fu, Da Wang, Weishen Shen, Baiyong |
author_sort | Li, Jingwei |
collection | PubMed |
description | PURPOSE: Pancreatic adenocarcinoma (PAAD) remains a highly aggressive gastrointestinal malignancy with a dismal prognosis. Pyroptosis has a key role in tumor development. Long noncoding RNAs (lncRNAs) are involved in tumorigenesis and pyroptosis regulation. However, the prognostic potential and function of pyroptosis-related lncRNAs (PRLs) in PAAD remain unclear. We aimed to identify PRLs with promising predictive value for PAAD prognosis and investigate the mechanism by which PRLs affect pyroptosis and PAAD development. METHODS: Key genes that regulate pyroptosis were determined from previous studies, and PRLs were identified from lncRNAs shown to be co-expressed in The Cancer Genome Atlas. Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model was used to establish a prognostic PRL signature. The clinical significance and functional mechanisms of LINC01133 were explored in vitro and in vivo. RESULTS: A seven-lncRNA signature was established and the high-risk subgroup exhibited a shorter survival time. With lower immune infiltration abundance, poor immune function, and higher tumor mutational burden (TMB), the high-risk subgroup reflected a more immunosuppressive status with a greater scope for benefiting from immunotherapy. After LINC01133 knockdown, PAAD cells showed lower viability and higher pyroptosis-related gene expression. LINC01133 functioned as a competing endogenous RNA to sequester miR-30b-5p from sponging SIRT1 mRNA to inhibit PAAD pyroptosis. CONCLUSION: With significant prognostic value, our PRL signature are involved in the biological processes of PAAD cells and associated with the immune environment. LINC01133 suppresses pyroptosis to promote PAAD development and could serve as a potential target for PAAD treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13402-023-00818-5. |
format | Online Article Text |
id | pubmed-10618383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-106183832023-11-02 A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis Li, Jingwei Lin, Jiewei Ji, Yuchen Wang, Xuelong Fu, Da Wang, Weishen Shen, Baiyong Cell Oncol (Dordr) Research PURPOSE: Pancreatic adenocarcinoma (PAAD) remains a highly aggressive gastrointestinal malignancy with a dismal prognosis. Pyroptosis has a key role in tumor development. Long noncoding RNAs (lncRNAs) are involved in tumorigenesis and pyroptosis regulation. However, the prognostic potential and function of pyroptosis-related lncRNAs (PRLs) in PAAD remain unclear. We aimed to identify PRLs with promising predictive value for PAAD prognosis and investigate the mechanism by which PRLs affect pyroptosis and PAAD development. METHODS: Key genes that regulate pyroptosis were determined from previous studies, and PRLs were identified from lncRNAs shown to be co-expressed in The Cancer Genome Atlas. Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model was used to establish a prognostic PRL signature. The clinical significance and functional mechanisms of LINC01133 were explored in vitro and in vivo. RESULTS: A seven-lncRNA signature was established and the high-risk subgroup exhibited a shorter survival time. With lower immune infiltration abundance, poor immune function, and higher tumor mutational burden (TMB), the high-risk subgroup reflected a more immunosuppressive status with a greater scope for benefiting from immunotherapy. After LINC01133 knockdown, PAAD cells showed lower viability and higher pyroptosis-related gene expression. LINC01133 functioned as a competing endogenous RNA to sequester miR-30b-5p from sponging SIRT1 mRNA to inhibit PAAD pyroptosis. CONCLUSION: With significant prognostic value, our PRL signature are involved in the biological processes of PAAD cells and associated with the immune environment. LINC01133 suppresses pyroptosis to promote PAAD development and could serve as a potential target for PAAD treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13402-023-00818-5. Springer Netherlands 2023-05-04 2023 /pmc/articles/PMC10618383/ /pubmed/37138146 http://dx.doi.org/10.1007/s13402-023-00818-5 Text en © The Author(s) 2023 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/) . |
spellingShingle | Research Li, Jingwei Lin, Jiewei Ji, Yuchen Wang, Xuelong Fu, Da Wang, Weishen Shen, Baiyong A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis |
title | A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis |
title_full | A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis |
title_fullStr | A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis |
title_full_unstemmed | A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis |
title_short | A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis |
title_sort | novel pyroptosis-associated lncrna linc01133 promotes pancreatic adenocarcinoma development via mir-30b-5p/sirt1 axis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618383/ https://www.ncbi.nlm.nih.gov/pubmed/37138146 http://dx.doi.org/10.1007/s13402-023-00818-5 |
work_keys_str_mv | AT lijingwei anovelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT linjiewei anovelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT jiyuchen anovelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT wangxuelong anovelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT fuda anovelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT wangweishen anovelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT shenbaiyong anovelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT lijingwei novelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT linjiewei novelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT jiyuchen novelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT wangxuelong novelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT fuda novelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT wangweishen novelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis AT shenbaiyong novelpyroptosisassociatedlncrnalinc01133promotespancreaticadenocarcinomadevelopmentviamir30b5psirt1axis |