Evidence map›Paper›PMID 40136417›Full record

ArticleCurrent issues in molecular biology2025

Lycobetaine Has Therapeutic Efficacy in Lung Squamous Cell Carcinoma by Targeting USP32 to Trigger Ferroptosis.

Shangping Xing, Hua Chai, Zhenlong Chen, Shuye Deng, Feifei Nong

Abstract read
In one paragraph

Article in Current issues in molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Shangping XingPharmaceutical College, Guangxi Medical University, Nanning 530021, China.
Hua ChaiPharmaceutical College, Guangxi Medical University, Nanning 530021, China.
Zhenlong ChenPharmaceutical College, Guangxi Medical University, Nanning 530021, China.
Shuye DengDepartment of Scientific Research, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530024, China.
Feifei NongDepartment of Scientific Research, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530024, China.

Funding

the National Natural Science Foundation of China 82460718the Natural Science Foundation of Guangxi Zhuang Autonomous Region 2023GXNSFBA026237the Natural Science Foundation of Guangxi Zhuang Autonomous Region 2024JJB140357
6 · The paper itself

Abstract

Ubiquitin-specific protease 32 (USP32), a deubiquitylating enzyme that controls the ubiquitin process, is overexpressed in multiple cancers and serves as a promising therapeutic target for cancer therapy. Drugs targeting ferroptosis have exhibited promising anticancer activity. Lycobetaine (LBT), a natural alkaloid, holds promise against various cancers, yet its specific targets and anticancer mechanisms remain unclear. In this study, we show that LBT induced ferroptosis in lung squamous cell carcinoma (LUSC) cells, accompanied by glutathione depletion and the accumulation of lipid peroxidation, malondialdehyde, and ferrous iron. Mechanistically, drug affinity responsive target stability-based mass spectrometry analysis, molecular dynamics simulations, and a cellular thermal shift assay confirmed that USP32 is a potential target of LBT in LUSC cells. Moreover, a strong interaction between USP32 and nuclear factor erythroid 2-related factor 2 (NRF2) was found via immunoprecipitation-mass spectrometry and co-immunoprecipitation. In addition, the ubiquitination assay results demonstrated that LBT treatment significantly increased NRF2 ubiquitination and degradation by targeting USP32. Importantly, USP32 overexpression effectively attenuated the effects of LBT on proliferation and ferroptosis in LUSC cells. In orthotopic LUSC xenografts, the administration of LBT significantly inhibited tumor growth and metastasis and induced ferroptosis by targeting the USP32-NRF2 signaling axis. Taken together, these data suggest that LBT exerts its anticancer effects by inhibiting USP32-mediated NRF2 deubiquitination to induce ferroptosis and that LBT may serve as a prospective USP32-targeting agent for LUSC treatment.

Indexed as

ferroptosisLUSClycobetaineNRF2ubiquitinationUSP32

Identifiers

PMID40136417
PMCPMC11941616

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.