{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:29:54Z","timestamp":1781483394991,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chief Scientist Research Project of Hubei Shizhen Laboratory","award":["HSL2024SX0006"],"award-info":[{"award-number":["HSL2024SX0006"]}]},{"name":"Key Scientific and Technological Project of Hubei Shizhen Laboratory","award":["SZL-2025-KT-06"],"award-info":[{"award-number":["SZL-2025-KT-06"]}]},{"name":"Talented Person Scientific Research Start-up Fund Subsidization Project of Chengdu University of Traditional Chinese Medicine","award":["030040015"],"award-info":[{"award-number":["030040015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Advanced lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths, with existing treatments hampered by drug resistance. This underscores the urgent need to identify novel therapeutic targets. The role of neuropeptide Y (NPY) receptors in LUAD remains unclear, and this study aimed to investigate their expression profiles, prognostic significance, and the antitumor potential of Euphorbia Factor L2 (EFL2). Methods: Bioinformatics analyses were performed to evaluate NPY receptors in LUAD. Lentivirus-mediated stable neuropeptide Y receptor 5 (NPY5R) knockdown, functional assays including CCK-8, flow cytometry, and scratch assay, PRESTO-Tango, RNA sequencing (RNA-seq), and qPCR were employed to validate the antitumor effects of EFL2 and the functional role of NPY5R. Results: High expression of NPY5R correlated with poor prognosis and immune cell infiltration in LUAD. EFL2 targeted NPY5R, inhibiting A549 cell proliferation and migration while inducing apoptosis. NPY5R knockdown further enhanced these antitumor effects, and the combination of NPY5R knockdown and EFL2 treatment synergistically enriched extracellular matrix (ECM), phosphatidylinositol 3-kinase (PI3K)-Akt, and mitogen-activated protein kinase (MAPK) pathways. Four potential molecular targets were identified. Conclusions: NPY5R is a promising therapeutic target for LUAD. While no clinical drugs targeting NPY5R are currently available, preclinical evidence supports its potential for anticancer drug development. EFL2 exerts antitumor effects via targeting NPY5R, offering useful guidance for developing novel LUAD therapies.<\/jats:p>","DOI":"10.3390\/ph19020322","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:37:28Z","timestamp":1771245448000},"page":"322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting NPY5R\u2014A Member of the NPY Receptor Family: Pharmacological and Transcriptomic Mechanisms of the Euphorbia Factor L2 Against Lung Adenocarcinoma"],"prefix":"10.3390","volume":"19","author":[{"given":"Pengzhuo","family":"Tao","sequence":"first","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Xue","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changmin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Fey","family":"Leu","sequence":"additional","affiliation":[{"name":"M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang 43000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3904-963X","authenticated-orcid":false,"given":"Chi","family":"Song","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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