Reversal of trastuzumab resistance in gastric cancer cells by targeting GPRC5A with miR-195-5p
10.12092/j.issn.1009-2501.2025.07.007
- VernacularTitle:miR-195-5p通过靶向GPRC5A逆转胃癌细胞对曲妥珠单抗的耐药性研究
- Author:
Xianjun ZHU
1
;
Danni ZHANG
;
Xijun LUO
;
Junjie LIANG
;
Tao LI
;
Xingkui TANG
;
Jialin HE
;
Wei LI
Author Information
1. 广州医科大学附属番禺中心医院普通外科,广州 510000,广东
- Publication Type:Journal Article
- Keywords:
gastric cancer;
miR-195-5p;
GPRC5A;
trastuzumab;
drug resistance;
molecular targeted therapy
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(7):929-934
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the role of miR-195-5p in mediating trastuzumab resistance in gastric cancer and to validate its potential as a therapeutic target along with its target gene GPRC5A.METH-ODS:Trastuzumab-resistant gastric cancer cell lines(NCI-N87 and MKN45)were established.Cell viabili-ty under trastuzumab treatment was assessed us-ing CCK-8 assays.Expression levels of miR-195-5p were determined by RT-qPCR.Transfection with miR-195-5p mimics was performed to evaluate changes in trastuzumab sensitivity and prolifera-tion.GPRC5A expression was also measured by RT-qPCR,and the targeting relationship between miR-195-5p and GPRC5A was confirmed using a dual-lu-ciferase reporter assay.RESULTS:Parental cells showed higher sensitivity to trastuzumab than re-sistant cells,with miR-195-5p expression signifi-cantly lower in the latter.Overexpression of miR-195-5p in resistant cells enhanced trastuzumab sen-sitivity and reduced proliferation.GPRC5A was found to be upregulated in resistant cells,and miR-195-5p directly targeted GPRC5A,affecting cell pro-liferation under trastuzumab treatment.CONCLU-SION:miR-195-5p may regulate trastuzumab sensi-tivity in gastric cancer by targeting GPRC5A,sug-gesting potential as a molecular marker for trastu-zumab therapy guidance.
