Cargando…
Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11
OBJECTIVE: Cholangiocarcinoma (CHOL) is a deadly cancer worldwide with limited available therapies. The aim of this study was to investigate key exosomal miRNAs and their functions in CHOL development. METHODS: Serum exosomes were isolated from patients with CHOL and healthy controls, followed by mi...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376483/ https://www.ncbi.nlm.nih.gov/pubmed/35978818 http://dx.doi.org/10.3389/fonc.2022.936507 |
_version_ | 1784768170515496960 |
---|---|
author | Gao, Huijie He, Zhaobin Gao, Chao Liu, Naiqing Zhang, Zhaoyang Niu, Weibo Niu, Jun Peng, Cheng |
author_facet | Gao, Huijie He, Zhaobin Gao, Chao Liu, Naiqing Zhang, Zhaoyang Niu, Weibo Niu, Jun Peng, Cheng |
author_sort | Gao, Huijie |
collection | PubMed |
description | OBJECTIVE: Cholangiocarcinoma (CHOL) is a deadly cancer worldwide with limited available therapies. The aim of this study was to investigate key exosomal miRNAs and their functions in CHOL development. METHODS: Serum exosomes were isolated from patients with CHOL and healthy controls, followed by miRNA sequencing for identifying differentially expressed miRNAs (DEMs) and their functions. Then, the expression of key DEMs was experimentally validated in exosomes from clinical CHOL patients and CHOL cells. The effects of overexpression of key DEMs on CHOL cell migration and proliferation were investigated. A key exosomal DEM miR-3124-5p was identified. The effects of overexpression or knockdown of exosomal miR-3124-5p on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were investigated. Moreover, the function of exosomal miR-3124-5p on tumor growth in vivo was explored. RESULTS: A total of 632 exosomal DEMs were identified between CHOL and control samples. Target genes of DEMs were significantly enriched in pathways, such as the p53 signaling pathway. miR-3124-5p was upregulated in serum exosomes from CHOL patients and exosomes from CHOL cells, and overexpression of miR-3124-5p promoted RBE cell migration and viability. Moreover, overexpression of exosomal miR-3124-5p promoted the proliferation, migration, and angiogenesis of HUVECs, while knockdown of miR-3124-5p had the opposite effect. miR-3124-5p could target growth differentiation factor 11 (GDF11) and downregulate GDF11 expression. Furthermore, exosomal miR-3124-5p promoted tumor growth in vivo. CONCLUSIONS: Our findings revealed that exosome-encapsulated miR-3124-5p promoted the malignant progression of CHOL by targeting GDF11. Exosomal miR-3124-5p and GDF11 could be promising biomarkers or therapeutic targets for CHOL. |
format | Online Article Text |
id | pubmed-9376483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93764832022-08-16 Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11 Gao, Huijie He, Zhaobin Gao, Chao Liu, Naiqing Zhang, Zhaoyang Niu, Weibo Niu, Jun Peng, Cheng Front Oncol Oncology OBJECTIVE: Cholangiocarcinoma (CHOL) is a deadly cancer worldwide with limited available therapies. The aim of this study was to investigate key exosomal miRNAs and their functions in CHOL development. METHODS: Serum exosomes were isolated from patients with CHOL and healthy controls, followed by miRNA sequencing for identifying differentially expressed miRNAs (DEMs) and their functions. Then, the expression of key DEMs was experimentally validated in exosomes from clinical CHOL patients and CHOL cells. The effects of overexpression of key DEMs on CHOL cell migration and proliferation were investigated. A key exosomal DEM miR-3124-5p was identified. The effects of overexpression or knockdown of exosomal miR-3124-5p on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were investigated. Moreover, the function of exosomal miR-3124-5p on tumor growth in vivo was explored. RESULTS: A total of 632 exosomal DEMs were identified between CHOL and control samples. Target genes of DEMs were significantly enriched in pathways, such as the p53 signaling pathway. miR-3124-5p was upregulated in serum exosomes from CHOL patients and exosomes from CHOL cells, and overexpression of miR-3124-5p promoted RBE cell migration and viability. Moreover, overexpression of exosomal miR-3124-5p promoted the proliferation, migration, and angiogenesis of HUVECs, while knockdown of miR-3124-5p had the opposite effect. miR-3124-5p could target growth differentiation factor 11 (GDF11) and downregulate GDF11 expression. Furthermore, exosomal miR-3124-5p promoted tumor growth in vivo. CONCLUSIONS: Our findings revealed that exosome-encapsulated miR-3124-5p promoted the malignant progression of CHOL by targeting GDF11. Exosomal miR-3124-5p and GDF11 could be promising biomarkers or therapeutic targets for CHOL. Frontiers Media S.A. 2022-08-01 /pmc/articles/PMC9376483/ /pubmed/35978818 http://dx.doi.org/10.3389/fonc.2022.936507 Text en Copyright © 2022 Gao, He, Gao, Liu, Zhang, Niu, Niu and Peng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Gao, Huijie He, Zhaobin Gao, Chao Liu, Naiqing Zhang, Zhaoyang Niu, Weibo Niu, Jun Peng, Cheng Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11 |
title | Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11 |
title_full | Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11 |
title_fullStr | Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11 |
title_full_unstemmed | Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11 |
title_short | Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11 |
title_sort | exosome-transmitted mir-3124-5p promotes cholangiocarcinoma development via targeting gdf11 |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376483/ https://www.ncbi.nlm.nih.gov/pubmed/35978818 http://dx.doi.org/10.3389/fonc.2022.936507 |
work_keys_str_mv | AT gaohuijie exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 AT hezhaobin exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 AT gaochao exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 AT liunaiqing exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 AT zhangzhaoyang exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 AT niuweibo exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 AT niujun exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 AT pengcheng exosometransmittedmir31245ppromotescholangiocarcinomadevelopmentviatargetinggdf11 |