Evidence map›Paper›PMID 35337344›Full record

ArticleJournal of biomedical science2022

Reprogramming of arachidonate metabolism confers temozolomide resistance to glioblastoma through enhancing mitochondrial activity in fatty acid oxidation.

Yu-Ting Tsai, Wei-Lun Lo, Pin-Yuan Chen, Chiung-Yuan Ko, Jian-Ying Chuang, Tzu-Jen Kao, Wen-Bing Yang, Kwang-Yu Chang, Chia-Yang Hung, Ushio Kikkawa and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.9field-weighted citation impact, top 3% 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

41 citing papers in PubMed, 55 citations in OpenAlex.

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  7. Unraveling the role of specificity protein 1 in gliomas: pathophysiology and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

12 authors at 5 institutions in 3 countries.

Yu-Ting Tsai *Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan, 110.
Wei-Lun Lo *Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
Pin-Yuan ChenSchool of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan.
Chiung-Yuan KoTMU Research Center of Neuroscience, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
Jian-Ying ChuangTMU Research Center of Neuroscience, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
Tzu-Jen KaoTMU Research Center of Neuroscience, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
Wen-Bing YangGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan, 110.
Kwang-Yu ChangNational Institute of Cancer Research, National Health Research Institutes, Tainan, 704, Taiwan.
Chia-Yang HungDepartment of Immuno-Oncology, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA.
Ushio KikkawaGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan, 110.
Wen-Chang ChangGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan, 110. wcchang@tmu.edu.tw.
Tsung-I HsuTMU Research Center of Neuroscience, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan. dabiemhsu@tmu.edu.tw.ORCID http://orcid.org/0000-0002-7524-7740
National Health Research Institutes · TWTaipei Medical University · TWChang Gung University · TWCity of Hope · USTaipei Medical University-Shuang Ho Hospital · TW

Funding

Ministry of Science and Technology, Taiwan MOST108-2320-B-038-012Ministry of Science and Technology, Taiwan MOST108-2628-B-038-005Ministry of Science and Technology, Taiwan MOST109-2320-B-038-065Ministry of Science and Technology, Taiwan MOST109-2320-B-182A-005-MY3Ministry of Science and Technology, Taiwan MOST109-2628-B-038-017Ministry of Science and Technology, Taiwan MOST110-2320-B-038-077-Ministry of Science and Technology, Taiwan MOST110-2628-B-038-021-Taipei Medical University 110TMU-SHH-16
6 · The paper itself

Abstract

backgroundSp1 is involved in the recurrence of glioblastoma (GBM) due to the acquirement of resistance to temozolomide (TMZ). Particularly, the role of Sp1 in metabolic reprogramming for drug resistance remains unknown.

methodsRNA-Seq and mass spectrometry were used to analyze gene expression and metabolites amounts in paired GBM specimens (primary vs. recurrent) and in paired GBM cells (sensitive vs. resistant). ω-3/6 fatty acid and arachidonic acid (AA) metabolism in GBM patients were analyzed by targeted metabolome. Mitochondrial functions were determined by Seahorse XF Mito Stress Test, RNA-Seq, metabolome and substrate utilization for producing ATP. Therapeutic options targeting prostaglandin (PG) E2 in TMZ-resistant GBM were validated in vitro and in vivo.

resultsAmong the metabolic pathways, Sp1 increased the prostaglandin-endoperoxide synthase 2 expression and PGE2 production in TMZ-resistant GBM. Mitochondrial genes and metabolites were obviously increased by PGE2, and these characteristics were required for developing resistance in GBM cells. For inducing TMZ resistance, PGE2 activated mitochondrial functions, including fatty acid β-oxidation (FAO) and tricarboxylic acid (TCA) cycle progression, through PGE2 receptors, E-type prostanoid (EP)1 and EP3. Additionally, EP1 antagonist ONO-8713 inhibited the survival of TMZ-resistant GBM synergistically with TMZ.

conclusionSp1-regulated PGE2 production activates FAO and TCA cycle in mitochondria, through EP1 and EP3 receptors, resulting in TMZ resistance in GBM. These results will provide us a new strategy to attenuate drug resistance or to re-sensitize recurred GBM.

Indexed as

GlioblastomaApoptosisCell Line, TumorDrug Resistance, NeoplasmFatty AcidsHumansMitochondriaTemozolomideFatty AcidsTemozolomideFatty acid β-oxidationMitochondriaPGE2Sp1TMZ-resistant GBM

Identifiers

PMID35337344
PMCPMC8952270
OpenAlexW4220701828

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.