miR-301a-3p induced by endoplasmic reticulum stress mediates the occurrence and transmission of trastuzumab resistance in HER2-positive gastric cancer.
miR-301a-3p induced by endoplasmic reticulum stress mediates the occurrence and transmission of trastuzumab resistance in HER2-positive gastric cancer.
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内质网应激诱导的miR-301a-3p介导HER2阳性胃癌曲妥珠单抗耐药的发生和传播
DOI：
10.1038/s41419-021-03991-3
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发表时间：
2021-07-13
影响因子：
9
通讯作者：
Zuo Q
中科院分区：
文献类型：
--
作者：
Guo J;Zhong X;Tan Q;Yang S;Liao J;Zhuge J;Hong Z;Deng Q;Zuo Q
曲妥珠单抗耐药对人表皮生长因子受体2（HER 2）阳性胃癌（GC）治疗的临床疗效产生负面影响，其潜在机制尚不清楚。因此，研究曲妥珠单抗耐药的机制，寻找有效的治疗方法是非常必要的。在此，我们证实了内质网（ER）应激通过上调HER 2阳性GC细胞中的miR-301 a-3 p诱导曲妥珠单抗耐药。此外，我们阐明了miR-301 a-3 p通过下调富含亮氨酸的重复序列和含有免疫球蛋白样结构域的蛋白1（LRIG 1）的表达，随后在ER应激下激活胰岛素样生长因子1受体（IGF-1 R）和成纤维细胞生长因子受体1（FGFR 1）的表达来介导曲妥珠单抗抗性。我们还发现miR-301 a-3 p通过外泌体的细胞间转移传播了曲妥珠单抗耐药性。本研究表明，外泌体miR-301 a-3 p可作为曲妥珠单抗耐药的非侵袭性生物标志物，可能成为克服曲妥珠单抗耐药、提高曲妥珠单抗治疗HER 2阳性胃癌疗效的一个新的潜在治疗靶点。
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.
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影响因子：
11.2
作者：
Miller, Jamie K.;Shattuck, David L.;Ingalla, Ellen Q.;Yen, Lily;Borowsky, Alexander D.;Young, Lawrence J. T.;Cardiff, Robert D.;Carraway, Kermit L., III;Sweeney, Colleen
通讯作者：
Sweeney, Colleen
影响因子：
--
作者：
Chen T;Xu XY;Zhou PH
通讯作者：
Zhou PH
影响因子：
64.5
作者：
Cubillos-Ruiz JR;Bettigole SE;Glimcher LH
通讯作者：
Glimcher LH
DOI：
10.3109/0284186x.2014.953258
发表时间：
2014-09
期刊：
Acta oncologica (Stockholm, Sweden)
影响因子：
--
作者：
Lindquist D;Kvarnbrink S;Henriksson R;Hedman H
通讯作者：
Hedman H
影响因子：
28.2
作者：
Pearson A;Smyth E;Babina IS;Herrera-Abreu MT;Tarazona N;Peckitt C;Kilgour E;Smith NR;Geh C;Rooney C;Cutts R;Campbell J;Ning J;Fenwick K;Swain A;Brown G;Chua S;Thomas A;Johnston SRD;Ajaz M;Sumpter K;Gillbanks A;Watkins D;Chau I;Popat S;Cunningham D;Turner NC
通讯作者：
Turner NC