What does this research mean for the field?

Euphorbia Factor L2 targets NPY5R, inhibiting lung adenocarcinoma cell proliferation and migration while inducing apoptosis, with NPY5R knockdown enhancing these antitumor effects. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

What question did this study set out to answer?

The study aims to explore the role of neuropeptide Y receptors in lung adenocarcinoma and assess the therapeutic potential of Euphorbia Factor L2.

February 17, 2026Open Access

Targeting NPY5R—A Member of the NPY Receptor Family: Pharmacological and Transcriptomic Mechanisms of the Euphorbia Factor L2 Against Lung Adenocarcinoma

Key Result

Euphorbia Factor L2 targets NPY5R, inhibiting LUAD A549 cell proliferation and migration while inducing apoptosis, with NPY5R knockdown enhancing these effects.

Key Points

The study aims to explore the role of neuropeptide Y receptors in lung adenocarcinoma and assess the therapeutic potential of Euphorbia Factor L2.
Conducted bioinformatics analyses of NPY receptors in lung adenocarcinoma
Performed lentivirus-mediated NPY5R knockdown
Executed functional assays including CCK-8, flow cytometry, and scratch assays
Utilized RNA sequencing and quantitative PCR to evaluate EFL2 antitumor effects
High NPY5R expression linked to poor prognosis and immune cell infiltration in LUAD
EFL2 inhibited A549 cell proliferation and migration while inducing apoptosis
NPY5R knockdown enhanced the antitumor effects of EFL2 treatment
Combination therapy enriched PI3K-Akt and MAPK pathways and extracellular matrix components

Structured PICO

Does Euphorbia Factor L2 targeting NPY5R inhibit lung adenocarcinoma cell proliferation and migration?

Population

Lung adenocarcinoma (LUAD) models including A549 cell line and bioinformatics datasets

Intervention

Euphorbia Factor L2 (EFL2) and/or lentivirus-mediated stable neuropeptide Y receptor 5 (NPY5R) knockdown

Comparator

Control (untreated or wild-type cells)

Outcome

Antitumor effects including cell proliferation, migration, and apoptosissurrogate

EFL2 exerts antitumor effects in lung adenocarcinoma by targeting NPY5R, highlighting NPY5R as a potential therapeutic target for anticancer drug development.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

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.