Cargando…

Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway

Globally, lung cancer remains one of the most prevalent malignant cancers. However, molecular mechanisms and functions involved in its pathogenesis have not been clearly elucidated. This study aimed to evaluate the specific regulatory mechanisms of exosomal miR-338-3p/CHL1/MAPK signaling pathway axi...

Descripción completa

Detalles Bibliográficos
Autores principales: Tian, Wen, Yang, Xianglin, Yang, He, Lv, Meiwen, Sun, Xinran, Zhou, Baosen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557210/
https://www.ncbi.nlm.nih.gov/pubmed/34718336
http://dx.doi.org/10.1038/s41419-021-04314-2
_version_ 1784592328822882304
author Tian, Wen
Yang, Xianglin
Yang, He
Lv, Meiwen
Sun, Xinran
Zhou, Baosen
author_facet Tian, Wen
Yang, Xianglin
Yang, He
Lv, Meiwen
Sun, Xinran
Zhou, Baosen
author_sort Tian, Wen
collection PubMed
description Globally, lung cancer remains one of the most prevalent malignant cancers. However, molecular mechanisms and functions involved in its pathogenesis have not been clearly elucidated. This study aimed to evaluate the specific regulatory mechanisms of exosomal miR-338-3p/CHL1/MAPK signaling pathway axis in non-small-cell lung cancer. Western blotting and qRT-PCR (reverse transcription-polymerase chain reaction) were used to determine the expression levels of CHL1 and exosomal miR-338-3p in NSCLC (non-small-cell lung cancer). The CHL1 gene was upregulated and downregulated to evaluate its functions in NSCLC progression. In vitro MTS and apoptotic assays were used to investigate the functions of CHL1 and exosomal miR-338-3p in NSCLC progression. The high-throughput sequencing was used to explore differently expressed exosomal miRNAs. The biological relationships between MAPK signaling pathway and CHL1 and exosomal miR-338-3p in NSCLC were predicted through bioinformatics analyses and verified by western blotting. Elevated CHL1 levels were observed in NSCLC tissues and cells. Upregulated CHL1 expression enhanced NSCLC cells’ progression by promoting tumor cells proliferation while suppressing their apoptosis. Conversely, the downregulation of the CHL1 gene inhibited NSCLC cells’ growth and promoted tumor cells’ apoptotic rate. Additionally, CHL1 activated the MAPK signaling pathway. Besides, we confirmed that miR-338-3p directly sponged with CHL1 to mediate tumor cells progression. Moreover, exosomal miR-338-3p serum levels in NSCLC patients were found to be low. BEAS-2B cells can transfer exosomal miR-338-3p to A549 cells and SK-MES-1 cells. In addition, elevated exosomal miR-338-3p levels significantly inhibited tumor cells proliferation and promoted their apoptosis by suppressing activation of the MAPK signaling pathway. Exosomal miR-338-3p suppresses tumor cells' metastasis by downregulating the expression of CHL1 through MAPK signaling pathway inactivation.
format Online
Article
Text
id pubmed-8557210
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-85572102021-11-15 Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway Tian, Wen Yang, Xianglin Yang, He Lv, Meiwen Sun, Xinran Zhou, Baosen Cell Death Dis Article Globally, lung cancer remains one of the most prevalent malignant cancers. However, molecular mechanisms and functions involved in its pathogenesis have not been clearly elucidated. This study aimed to evaluate the specific regulatory mechanisms of exosomal miR-338-3p/CHL1/MAPK signaling pathway axis in non-small-cell lung cancer. Western blotting and qRT-PCR (reverse transcription-polymerase chain reaction) were used to determine the expression levels of CHL1 and exosomal miR-338-3p in NSCLC (non-small-cell lung cancer). The CHL1 gene was upregulated and downregulated to evaluate its functions in NSCLC progression. In vitro MTS and apoptotic assays were used to investigate the functions of CHL1 and exosomal miR-338-3p in NSCLC progression. The high-throughput sequencing was used to explore differently expressed exosomal miRNAs. The biological relationships between MAPK signaling pathway and CHL1 and exosomal miR-338-3p in NSCLC were predicted through bioinformatics analyses and verified by western blotting. Elevated CHL1 levels were observed in NSCLC tissues and cells. Upregulated CHL1 expression enhanced NSCLC cells’ progression by promoting tumor cells proliferation while suppressing their apoptosis. Conversely, the downregulation of the CHL1 gene inhibited NSCLC cells’ growth and promoted tumor cells’ apoptotic rate. Additionally, CHL1 activated the MAPK signaling pathway. Besides, we confirmed that miR-338-3p directly sponged with CHL1 to mediate tumor cells progression. Moreover, exosomal miR-338-3p serum levels in NSCLC patients were found to be low. BEAS-2B cells can transfer exosomal miR-338-3p to A549 cells and SK-MES-1 cells. In addition, elevated exosomal miR-338-3p levels significantly inhibited tumor cells proliferation and promoted their apoptosis by suppressing activation of the MAPK signaling pathway. Exosomal miR-338-3p suppresses tumor cells' metastasis by downregulating the expression of CHL1 through MAPK signaling pathway inactivation. Nature Publishing Group UK 2021-10-30 /pmc/articles/PMC8557210/ /pubmed/34718336 http://dx.doi.org/10.1038/s41419-021-04314-2 Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tian, Wen
Yang, Xianglin
Yang, He
Lv, Meiwen
Sun, Xinran
Zhou, Baosen
Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway
title Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway
title_full Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway
title_fullStr Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway
title_full_unstemmed Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway
title_short Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway
title_sort exosomal mir-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting chl1 through the mapk signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557210/
https://www.ncbi.nlm.nih.gov/pubmed/34718336
http://dx.doi.org/10.1038/s41419-021-04314-2
work_keys_str_mv AT tianwen exosomalmir3383psuppressesnonsmallcelllungcancercellsmetastasisbyinhibitingchl1throughthemapksignalingpathway
AT yangxianglin exosomalmir3383psuppressesnonsmallcelllungcancercellsmetastasisbyinhibitingchl1throughthemapksignalingpathway
AT yanghe exosomalmir3383psuppressesnonsmallcelllungcancercellsmetastasisbyinhibitingchl1throughthemapksignalingpathway
AT lvmeiwen exosomalmir3383psuppressesnonsmallcelllungcancercellsmetastasisbyinhibitingchl1throughthemapksignalingpathway
AT sunxinran exosomalmir3383psuppressesnonsmallcelllungcancercellsmetastasisbyinhibitingchl1throughthemapksignalingpathway
AT zhoubaosen exosomalmir3383psuppressesnonsmallcelllungcancercellsmetastasisbyinhibitingchl1throughthemapksignalingpathway