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Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma
OBJECTIVE: SPON2 is one of the extracellular matrix proteins, which is closely related to the progression of a variety of tumors including non-small cell lung cancer (NSCLC), but its upstream regulation mechanism remains unclear. Our research aims to find the specific regulatory pathway of SPON2 by...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509512/ https://www.ncbi.nlm.nih.gov/pubmed/36153414 http://dx.doi.org/10.1007/s12672-022-00553-7 |
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author | Chen, Zhipeng Bian, Chengyu Huang, Jingjing Li, Xiang Chen, Liang Xie, Xueying Xia, Yang Yin, Rong Wang, Jun |
author_facet | Chen, Zhipeng Bian, Chengyu Huang, Jingjing Li, Xiang Chen, Liang Xie, Xueying Xia, Yang Yin, Rong Wang, Jun |
author_sort | Chen, Zhipeng |
collection | PubMed |
description | OBJECTIVE: SPON2 is one of the extracellular matrix proteins, which is closely related to the progression of a variety of tumors including non-small cell lung cancer (NSCLC), but its upstream regulation mechanism remains unclear. Our research aims to find the specific regulatory pathway of SPON2 by exploring the potential crosstalk between tumor cells and cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME) of NSCLC. METHODS: We analyzed T1 lung adenocarcinoma samples from TCGA and screened extracellular matrix proteins that indicate poor prognosis. Expression level of SPON2 was verified by qPCR in clinical samples. The exosomes of NSCLC cell supernatant were extracted and identified by nanoparticle tracking analysis (NTA) and transmission electron microscope, western blots. The exosomes and CAFs were co-cultured, and cell migration and Matrigel invasion assay were used to evaluate the effect of CAFs on the migration and invasion of NSCLC cells. The interaction between LncRNA and miRNA was verified by Targetscan prediction, luciferase reporter assay, and RNA binding protein immunoprecipitation (RIP). RESULTS: We found that the expression of SPON2 was up-regulated in clinical T1a stage NSCLC patients. The expression of lnc HOTAIRM1 (HOTAIRM1) in exosomes secreted by NSCLC tissues increased. After exosomal HOTAIRM1 entered CAFs, HOTAIRM1 can adsorb miR-328-5p to up-regulate the expression of SPON2 in CAFs. Up-regulation of SPON2 in CAFs could promote the migration and invasion of NSCLC cells. CONCLUSION: Tumor-derived exosomal HOTAIRM1 can transfer into CAFs and competitively adsorb miR-328-5p, and regulate the SPON2 expression of CAFs cells, ultimately promote the progression of NSCLC. The discovery of this regulatory pathway can provide a new potential therapeutic target for the diagnosis and treatment of NSCLC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-022-00553-7. |
format | Online Article Text |
id | pubmed-9509512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-95095122022-09-26 Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma Chen, Zhipeng Bian, Chengyu Huang, Jingjing Li, Xiang Chen, Liang Xie, Xueying Xia, Yang Yin, Rong Wang, Jun Discov Oncol Research OBJECTIVE: SPON2 is one of the extracellular matrix proteins, which is closely related to the progression of a variety of tumors including non-small cell lung cancer (NSCLC), but its upstream regulation mechanism remains unclear. Our research aims to find the specific regulatory pathway of SPON2 by exploring the potential crosstalk between tumor cells and cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME) of NSCLC. METHODS: We analyzed T1 lung adenocarcinoma samples from TCGA and screened extracellular matrix proteins that indicate poor prognosis. Expression level of SPON2 was verified by qPCR in clinical samples. The exosomes of NSCLC cell supernatant were extracted and identified by nanoparticle tracking analysis (NTA) and transmission electron microscope, western blots. The exosomes and CAFs were co-cultured, and cell migration and Matrigel invasion assay were used to evaluate the effect of CAFs on the migration and invasion of NSCLC cells. The interaction between LncRNA and miRNA was verified by Targetscan prediction, luciferase reporter assay, and RNA binding protein immunoprecipitation (RIP). RESULTS: We found that the expression of SPON2 was up-regulated in clinical T1a stage NSCLC patients. The expression of lnc HOTAIRM1 (HOTAIRM1) in exosomes secreted by NSCLC tissues increased. After exosomal HOTAIRM1 entered CAFs, HOTAIRM1 can adsorb miR-328-5p to up-regulate the expression of SPON2 in CAFs. Up-regulation of SPON2 in CAFs could promote the migration and invasion of NSCLC cells. CONCLUSION: Tumor-derived exosomal HOTAIRM1 can transfer into CAFs and competitively adsorb miR-328-5p, and regulate the SPON2 expression of CAFs cells, ultimately promote the progression of NSCLC. The discovery of this regulatory pathway can provide a new potential therapeutic target for the diagnosis and treatment of NSCLC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-022-00553-7. Springer US 2022-09-24 /pmc/articles/PMC9509512/ /pubmed/36153414 http://dx.doi.org/10.1007/s12672-022-00553-7 Text en © The Author(s) 2022 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 Chen, Zhipeng Bian, Chengyu Huang, Jingjing Li, Xiang Chen, Liang Xie, Xueying Xia, Yang Yin, Rong Wang, Jun Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma |
title | Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma |
title_full | Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma |
title_fullStr | Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma |
title_full_unstemmed | Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma |
title_short | Tumor-derived exosomal HOTAIRM1 regulates SPON2 in CAFs to promote progression of lung adenocarcinoma |
title_sort | tumor-derived exosomal hotairm1 regulates spon2 in cafs to promote progression of lung adenocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509512/ https://www.ncbi.nlm.nih.gov/pubmed/36153414 http://dx.doi.org/10.1007/s12672-022-00553-7 |
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