Evidence map›Paper›PMID 40462127›Full record

ArticleLipids in health and disease2025

TNFα activation of the PLEKHA5-FCRLA axis disturbs lipid metabolism, leading to the progression of cutaneous malignant melanoma.

Kexin Yan, Wei Zhang, Wenqi Chu, Jinliang Qi, Hao Song, Xiulian Xu

Abstract read
In one paragraph

Article in Lipids in health and disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

6 authors.

Kexin YanHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Nanjing, China.
Wei ZhangHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Nanjing, China.
Wenqi ChuHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Nanjing, China.
Jinliang QiState Key Laboratory of Pharmaceutical Biotechnology, Institute for Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, China. QiJL@nju.edu.cn.
Hao SongHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Nanjing, China. songhao199005@163.com.
Xiulian XuHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Nanjing, China. xxlqjl@sina.com.

Funding

National Key Research and Development Program of China 2022YFC3601800National Natural Science Foundation of China 81772916National Natural Science Foundation of China 82103470Natural Science Foundation of Jiangsu Province BK20171132Natural Science Foundation of Tibet Autonomous Region XZ2021ZR-ZY12(Z)
6 · The paper itself

Abstract

backgroundCutaneous malignant melanoma (CMM) ranks among the deadliest forms of cancer. Abnormalities in lipid metabolism may have a connection with the risk of CMM progression.

methodsLipid metabolism-related genes were selected in MSigDB. A lipid metabolism-related predictive model was constructed in The Cancer Genome Atlas-skin cutaneous melanoma (TCGA-SKCM) using univariate Cox regression analysis, non-negative matrix factorization (NMF) clustering analysis, Weighted correlation network analysis (WGCNA), least absolute shrinkage and selection operator regression (LASSO) analysis, and outcomes-related genes were identified. The roles of candidate genes in CMM were determined using in vivo and in vitro experiments, and the pathway mechanism of the candidate gene was studied using transcriptomics, proteomics, lipid metabolomics, and other molecular biological methods.

resultsA predictive model was established, Risk Score = -0.009 * UBE2L6 + 0.033 * PLEKHA5 + 0.024 * LHB + 0.036 * CARM1 + 0.016 * PRXL2B + 0.131 * PLA2G4D. The pleckstrin homology domain-containing A5 (PLEKHA5) was identified as an essential gene and positively correlated with poor outcomes in CMM. Fc receptor-like A (FCRLA) is the downstream gene of PLEKHA5, upregulated in CMM, and tumor necrosis factor alpha (TNFα) is also an essential cytokine that promotes CMM proliferation and metastasis. Lipid metabolomics showed that PLEKHA5 knockdown increased ceramide and sphingosine levels while decreasing cholesterol ester and triglyceride levels in CMM cells, possibly related to disease progression.

conclusionThe predictive model of CMM related to lipid metabolism was constructed. TNFα activates the PLEKHA5-FCRLA axis to enhance neutral lipid storage and energy metabolism in CMM cells, promoting malignant behavior.

Indexed as

Lipid MetabolismMelanomaSkin NeoplasmsTumor Necrosis Factor-alphaAnimalsCell Line, TumorCutaneous Malignant MelanomaDisease ProgressionGene Expression Regulation, NeoplasticHumansMiceTumor Necrosis Factor-alphaCutaneous malignant melanomaLipid metabolismOncogeneRisk model

Identifiers

PMID40462127
PMCPMC12131485

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.