Evidence map›Paper›PMID 39390559›Full record

ArticleJournal of translational medicine2024

KLF14 directly downregulates the expression of GPX4 to exert antitumor effects by promoting ferroptosis in cervical cancer.

Hui Ye, XuChao Ding, XinRan Lv, Ying Du, Rui Guo, Jin Qiu, RuoNan Li, LiLi Cao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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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

8 authors.

Hui YeOncology Department, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, 250014, China.
XuChao DingDepartment of Blood Transfusion, Binzhou People's Hospital, Binzhou, 256601, China.
XinRan LvShandong Public Health Clinical Center, Shandong University, Shandong, 250013, China.
Ying DuDepartment of Laboratory Medicine, Linyi Peoples' Hospital, Linyi, 276003, China.
Rui GuoDepartment of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.
Jin QiuOncology Department, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.
RuoNan LiOncology Department, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.
LiLi CaoOncology Department, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, 250014, China. llcao@sdfmu.edu.cn.

Funding

shandong provincial natural science foundation ZR2020MH203
6 · The paper itself

Abstract

backgroundCervical cancer is the fourth leading cause of cancer-related death among women worldwide, and effective therapeutic strategies for its treatment are limited. Recent studies have indicated that ferroptosis, a form of regulated cell death, is a promising therapeutic strategy. KLF14 has been shown to regulate both cell proliferation and apoptosis in cervical cancer. However, its role in modulating lipid peroxidation and ferroptosis remains largely unexplored and enigmatic.

methodsSiHa and HeLa cells were transduced with lentiviral vectors to overexpress KLF14. Protein levels were analyzed via western blotting and immunohistochemistry (IHC). LDH assays, calcein-AM/propidium iodide (PI) staining, and generation of cell growth curves using a real-time cell analysis (RTCA) system were used to detect cell damage and proliferation. Cellular ROS, lipid ROS, transmission electron microscopy (TEM), and Fe

resultsKLF14 is abnormally expressed in various tumors and downregulated in cervical cancer. Overexpression of KLF14 induced ferroptosis and inhibited cell proliferation in vitro as well as xenograft tumorigenicity in vivo. Mechanistic studies revealed that KLF14 binds to the promoter of GPX4, suppressing its transcriptional activity and thereby decreasing its expression, which contributes to the induction of ferroptosis. Truncation and point mutation analyses of the GPX4 promoter revealed multiple binding sites for KLF14 within the - 1000 bp to + 35 bp region, which are responsible for its inhibitory effect on GPX4 transcription. Additionally, deletion of the zinc finger motif in KLF14 abolished its inhibitory effect on GPX4 promoter activity and cell proliferation.

conclusionOur data revealed a previously unidentified function of KLF14 in promoting ferroptosis, which results in the suppression of cell proliferation. Mechanistically, we revealed a novel regulatory mechanism by which KLF14 targets GPX4. These findings suggest a novel strategy to induce ferroptosis through the targeting of KLF14 in human cervical cancer cells.

Indexed as

Cell ProliferationDown-RegulationFerroptosisGene Expression Regulation, NeoplasticKruppel-Like Transcription FactorsPhospholipid Hydroperoxide Glutathione PeroxidaseUterine Cervical NeoplasmsAnimalsBase SequenceCell Line, TumorFemaleHeLa CellsHumansMiceMice, NudePromoter Regions, GeneticGPX4 protein, humanKLF14 protein, humanKruppel-Like Transcription FactorsPhospholipid Hydroperoxide Glutathione PeroxidaseReactive Oxygen SpeciesCervical cancerFerroptosisGPX4KLF14PromoterTranscription factor

Identifiers

PMID39390559
PMCPMC11465826

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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 OpenQuestion graph.