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Updated: Aug 25, 2025
Author Spotlight: Establishing a Murine Non-Small Cell Lung Cancer Model for Developing Nanoformulations of Anticancer Drugs
Published on: May 10, 2024
Screening of the siGPCR library in combination with cisplatin against lung cancers
Youngju Kim1, Jieun Lee1, Sumin Jeong1
1Department of Biological Sciences, Sookmyung Women's University, Science building 404, Cheongpa-ro 47-gil 100, Yongsan-gu, Seoul, 04310, Republic of Korea.
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.
Insights
Researchers identified G protein-coupled receptors (GPCRs) that enhance cisplatin
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- G protein-coupled receptors (GPCRs) play diverse roles in cellular processes.
- Cisplatin is a widely used chemotherapy agent for lung cancer.
- Identifying novel targets to enhance cisplatin efficacy is crucial for improving patient outcomes.
Purpose of the Study:
- To screen for G protein-coupled receptors (GPCRs) that modulate lung cancer cell response to cisplatin.
- To identify specific GPCRs that enhance cisplatin's anti-cancer effects.
- To validate potential GPCR targets for combination therapy.
Main Methods:
- Multiplexed siRNA screening of 390 human GPCRs in lung cancer cells treated with cisplatin.
- Direct cell counting to assess anti-cancer effects.
- On-target validation of identified GPCRs.
- Q-omics analysis of GPCR expression and patient survival data.
Main Results:
- Direct cell count identified 46 GPCRs with significant growth inhibition (>twofold, p < 0.01).
- siRNAs targeting ADRA2A, F2RL3, NPSR1, NPY, and TACR3 enhanced cisplatin's anti-proliferation efficacy.
- Knockdown of TACR3 demonstrated anti-cancer efficacy in both single and combination treatments.
- High TACR3 expression correlated with unfavorable patient survival, especially with GPCR pathway mutations.
Conclusions:
- The study identified several GPCRs as potential targets to enhance cisplatin chemotherapy in lung cancer.
- TACR3 emerged as a promising target, with its knockdown showing anti-cancer effects and high expression linked to poor prognosis.
- The findings provide a valuable resource for developing novel combination therapies and biomarkers for lung cancer treatment.
