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MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer
The immune checkpoint ligand programmed death-ligand 1 (PD-L1) and the transmembrane mucin (MUC) 3A are upregulated in non-small cell lung cancer (NSCLC), contributing to the aggressive pathogenesis and poor prognosis. Here, we report that knocking down the oncogenic MUC3A suppresses the PD-L1 expre...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120466/ https://www.ncbi.nlm.nih.gov/pubmed/33994852 http://dx.doi.org/10.7150/ijbs.57964 |
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author | Luo, Yuan Ma, Shijing Sun, Yingming Peng, Shan Zeng, Zihang Han, Linzhi Li, Shuying Sun, Wenjie Xu, Jieyu Tian, Xiaoli Wang, Feng Wu, Qiuji Xiao, Yu Zhang, Junhong Gong, Yan Xie, Conghua |
author_facet | Luo, Yuan Ma, Shijing Sun, Yingming Peng, Shan Zeng, Zihang Han, Linzhi Li, Shuying Sun, Wenjie Xu, Jieyu Tian, Xiaoli Wang, Feng Wu, Qiuji Xiao, Yu Zhang, Junhong Gong, Yan Xie, Conghua |
author_sort | Luo, Yuan |
collection | PubMed |
description | The immune checkpoint ligand programmed death-ligand 1 (PD-L1) and the transmembrane mucin (MUC) 3A are upregulated in non-small cell lung cancer (NSCLC), contributing to the aggressive pathogenesis and poor prognosis. Here, we report that knocking down the oncogenic MUC3A suppresses the PD-L1 expression in NSCLC cells. MUC3A is a potent regulator of epidermal growth factor receptor (EGFR) stability, and MUC3A deficiency downregulates the activation of the PI3K/Akt and MAPK pathways, which subsequently reduces the expression of PD-L1. Furthermore, knockdown of MUC3A and tyrosine kinase inhibitors (TKIs) in EGFR-mutant NSCLC cells play a synergistic effect on inhibited proliferation and promoted apoptosis in vitro. In the BALB/c nude mice xenograft model, MUC3A deficiency enhances EGFR-mutated NSCLC sensitivity to TKIs. Our study shows that transmembrane mucin MUC3A induces PD-L1, thereby promoting immune escape in NSCLC, while downregulation of MUC3A enhances TKIs effects in EGFR-mutant NSCLC. These findings offer insights into the design of novel combination treatment for NSCLC. |
format | Online Article Text |
id | pubmed-8120466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-81204662021-05-14 MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer Luo, Yuan Ma, Shijing Sun, Yingming Peng, Shan Zeng, Zihang Han, Linzhi Li, Shuying Sun, Wenjie Xu, Jieyu Tian, Xiaoli Wang, Feng Wu, Qiuji Xiao, Yu Zhang, Junhong Gong, Yan Xie, Conghua Int J Biol Sci Research Paper The immune checkpoint ligand programmed death-ligand 1 (PD-L1) and the transmembrane mucin (MUC) 3A are upregulated in non-small cell lung cancer (NSCLC), contributing to the aggressive pathogenesis and poor prognosis. Here, we report that knocking down the oncogenic MUC3A suppresses the PD-L1 expression in NSCLC cells. MUC3A is a potent regulator of epidermal growth factor receptor (EGFR) stability, and MUC3A deficiency downregulates the activation of the PI3K/Akt and MAPK pathways, which subsequently reduces the expression of PD-L1. Furthermore, knockdown of MUC3A and tyrosine kinase inhibitors (TKIs) in EGFR-mutant NSCLC cells play a synergistic effect on inhibited proliferation and promoted apoptosis in vitro. In the BALB/c nude mice xenograft model, MUC3A deficiency enhances EGFR-mutated NSCLC sensitivity to TKIs. Our study shows that transmembrane mucin MUC3A induces PD-L1, thereby promoting immune escape in NSCLC, while downregulation of MUC3A enhances TKIs effects in EGFR-mutant NSCLC. These findings offer insights into the design of novel combination treatment for NSCLC. Ivyspring International Publisher 2021-04-12 /pmc/articles/PMC8120466/ /pubmed/33994852 http://dx.doi.org/10.7150/ijbs.57964 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Luo, Yuan Ma, Shijing Sun, Yingming Peng, Shan Zeng, Zihang Han, Linzhi Li, Shuying Sun, Wenjie Xu, Jieyu Tian, Xiaoli Wang, Feng Wu, Qiuji Xiao, Yu Zhang, Junhong Gong, Yan Xie, Conghua MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer |
title | MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer |
title_full | MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer |
title_fullStr | MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer |
title_full_unstemmed | MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer |
title_short | MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer |
title_sort | muc3a induces pd-l1 and reduces tyrosine kinase inhibitors effects in egfr-mutant non-small cell lung cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120466/ https://www.ncbi.nlm.nih.gov/pubmed/33994852 http://dx.doi.org/10.7150/ijbs.57964 |
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