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miR-301a-3p induced by endoplasmic reticulum stress mediates the occurrence and transmission of trastuzumab resistance in HER2-positive gastric cancer.

Authors :
Guo J
Zhong X
Tan Q
Yang S
Liao J
Zhuge J
Hong Z
Deng Q
Zuo Q
Source :
Cell death & disease [Cell Death Dis] 2021 Jul 13; Vol. 12 (7), pp. 696. Date of Electronic Publication: 2021 Jul 13.
Publication Year :
2021

Abstract

Trastuzumab resistance negatively influences the clinical efficacy of the therapy for human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC), and the underlying mechanisms remain elusive. Exploring the mechanisms and finding effective approaches to address trastuzumab resistance are of great necessity. Here, we confirmed that endoplasmic reticulum (ER) stress-induced trastuzumab resistance by up-regulating miR-301a-3p in HER2-positive GC cells. Moreover, we elucidated that miR-301a-3p mediated trastuzumab resistance by down-regulating the expression of leucine-rich repeats and immunoglobulin-like domains containing protein 1 (LRIG1) and subsequently activating the expression of insulin-like growth factor 1 receptor (IGF-1R) and fibroblast growth factor receptor 1 (FGFR1) under ER stress. We also found that intercellular transfer of miR-301a-3p by exosomes disseminated trastuzumab resistance. The present study demonstrated that exosomal miR-301a-3p could serve as a non-invasive biomarker for trastuzumab resistance, which was maybe a novel potential therapeutic target to overcome trastuzumab resistance and improve the curative effect of trastuzumab in HER2-positive GC patients.<br /> (© 2021. The Author(s).)

Details

Language :
English
ISSN :
2041-4889
Volume :
12
Issue :
7
Database :
MEDLINE
Journal :
Cell death & disease
Publication Type :
Academic Journal
Accession number :
34257270
Full Text :
https://doi.org/10.1038/s41419-021-03991-3