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Screening of the siGPCR library in combination with cisplatin against lung cancersopen access

Authors
Kim, YoungjuLee, JieunJeong, SuminKim, Woo-YoungJeong, EunaYoon, Sukjoon
Issue Date
Oct-2022
Publisher
NATURE PORTFOLIO
Citation
SCIENTIFIC REPORTS, v.12, no.1
Journal Title
SCIENTIFIC REPORTS
Volume
12
Number
1
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/152383
DOI
10.1038/s41598-022-21063-0
ISSN
2045-2322
Abstract
The screening of siRNAs targeting 390 human G protein-coupled receptors (GPCRs) was multiplexed in combination with cisplatin against lung cancer cells. While the cell viability measure hardly captured the anticancer effect of siGPCRs, the direct cell count revealed the anticancer potential of diverse GPCRs (46 hits with >twofold growth inhibition, p-value <0.01). In combined treatment with cisplatin, siRNAs against five genes (ADRA2A, F2RL3, NPSR1, NPY and TACR3) enhanced the anti-proliferation efficacy on cancer cells and reduced the self-recovery ability of surviving cells after the removal of the combined treatment. Further on-target validation confirmed that the knockdown of TACR3 expression exhibited anticancer efficacy under both single and combined treatment with cisplatin. Q-omics (http://qomics.io) analysis showed that high expression of TACR3 was unfavorable for patient survival, particularly with mutations in GPCR signaling pathways. The present screening data provide a useful resource for GPCR targets and biomarkers for improving the efficacy of cisplatin treatment.
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이과대학 (생명시스템학부)
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