Evidence map›Paper›PMID 36423520›Full record

ArticleRedox biology2022

HDLBP-stabilized lncFAL inhibits ferroptosis vulnerability by diminishing Trim69-dependent FSP1 degradation in hepatocellular carcinoma.

Jingsheng Yuan, Tao Lv, Jian Yang, Zhenru Wu, Lvnan Yan, Jiayin Yang, Yujun Shi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

53 citing papers in PubMed, 83 citations in OpenAlex.

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  15. Epigenetic regulation of ferroptosis in gastrointestinal cancers (Review).International journal of molecular medicine · 2025
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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

7 authors at 1 institution in 1 country.

Jingsheng YuanDepartment of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, 610041, China.
Tao LvDepartment of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, 610041, China.
Jian YangDepartment of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, 610041, China.
Zhenru WuLaboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu, 610041, China.
Lvnan YanDepartment of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, 610041, China.
Jiayin YangDepartment of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, 610041, China. Electronic address: doctoryjy@scu.edu.cn.
Yujun ShiLaboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu, 610041, China. Electronic address: shiyujun@scu.edu.cn.
Sichuan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent studies have suggested that exploring the potential mechanisms regulating ferroptosis vulnerability may contribute to improving the systemic therapeutic efficacy in HCC. High-density lipoprotein-binding protein (HDLBP), the largest RNA-binding protein, is an important transporter that protects cells from overaccumulation of cholesterol, but few studies have elucidated the role of HDLBP in the regulation of ferroptosis vulnerability in HCC. Our study suggests that HDLBP was markedly elevated in HCC compared with noncancerous liver tissues and that this elevation inhibited the ferroptosis vulnerability of HCC. Further experiments revealed that HDLBP bound to and stabilized the long noncoding RNA lncFAL (ferroptosis-associated lncRNA), which is derived from the plexin B2 gene. Moreover, our study suggests that the splicing of lncFAL was increased by YTH N6-methyladenosine (m6A) RNA-binding protein 2 (YTHDF2) in a m6A-dependent manner. Although HDLBP or lncFAL could not regulate the GPX4 antioxidant signalling pathway, lncFAL reduced ferroptosis vulnerability by directly binding to ferroptosis suppressor protein 1 (FSP1) and competitively abolishing Trim69-dependent FSP1 polyubiquitination degradation. More importantly, FSP1 inhibition promoted the antitumour activity of ferroptosis inducers both in vitro and in vivo. Collectively, our results provide a clinically promising demonstration that HDLBP stabilizes lncFAL, which mediates a FSP1-dependent anti-ferroptosis mechanism in HCC. These results support the enormous potential of disrupting FSP1 as a promising therapeutic approach for HCC patients with high HDLBP or lncFAL expression.

Indexed as

Carcinoma, HepatocellularFerroptosisLiver NeoplasmsRNA, Long NoncodingApoptosis Regulatory ProteinsHumansMitochondrial ProteinsRNA-Binding ProteinsTripartite Motif ProteinsUbiquitin-Protein LigasesApoptosis Regulatory Proteinsferroptosis suppressor protein 1, humanhigh density lipoprotein binding proteinMitochondrial ProteinsRNA-Binding ProteinsRNA, Long NoncodingTRIM69 protein, humanTripartite Motif ProteinsUbiquitin-Protein LigasesFerroptosisFSP1HDLBPHepatocellular carcinomalncRNAUbiquitination

Identifiers

PMID36423520
PMCPMC9692041
OpenAlexW4309672501

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.