Evidence map›Paper›PMID 42029117›Full record

ArticleThoracic cancer2026

BMAL1 Drives Cisplatin Resistance in Non-Small Cell Lung Cancer Via Lactate-MRP1 Signaling Pathway.

Zixin Shi, Ziniu Qin, Chuantao Chen, Xiaolin Yang, Yunhan Hu, Xiaohui Meng, Yuxiang Cao, Xiang Tao, Zhijian Zhang, Tiancheng Xie and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Thoracic cancer, 2026. 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
–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

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

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

12 authors.

Zixin ShiResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Ziniu QinResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Chuantao ChenResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Xiaolin YangResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Yunhan HuResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Xiaohui MengResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Yuxiang CaoResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Xiang TaoResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Zhijian ZhangResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Tiancheng XieResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Huijun WeiResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.
Zhihao WuResearch Laboratory of Tumor Microenvironment, Wannan Medical University, Wuhu, China.ORCID https://orcid.org/0000-0001-8368-5129

Funding

2023 Annual Key Project Research Fund of Wannan Medical College WK2023ZZD13Anhui Provincial Key Science Foundation for Outstanding Young Talent 23AH030108Health Science Research Project of Anhui Province AHWJ2022a028National College Students Innovation and Entrepreneurship Training Program 202110368065National College Students Innovation and Entrepreneurship Training Program 202310368018National College Students Innovation and Entrepreneurship Training Program 202510368009National Natural Science Foundation of China 81872371Natural Science Foundation of the Higher Education Institutions of Anhui Province 2025AHGXZK30247Program for Excellent Sci-tech Innovation Teams of Universities in Anhui Province 2023AH010073Provincial-level Quality Project in Higher Education Institutions of Anhui Province 2022jyxm1710
6 · The paper itself

Abstract

Lung cancer, the leading cause of cancer-related mortality, faces significant therapeutic challenges due to chemoresistance. While metabolic reprogramming and circadian disruptions are implicated in tumor progression, their interplay in driving resistance remains unclear. This study identifies BMAL1, a core circadian regulator, as a key driver and potential initiator of cisplatin resistance in non-small cell lung cancer (NSCLC) through metabolic and oxidative stress pathways. We demonstrate that BMAL1 upregulates multidrug resistance protein MRP1 via HIF-1α-driven glycolysis, amplifying lactate production. Lactate activates the TAZ/c-Jun/Snail complex to increase MRP1 expression, establishing a feedforward loop that sustains chemoresistance. Furthermore, cisplatin and etoposide induce BMAL1 expression through AKT signaling in response to oxidative stress, creating a self-reinforcing resistance mechanism. Critically, targeting AKT or MRP1 reverses BMAL1-mediated resistance. These findings reveal BMAL1 as a metabolic orchestrator linking circadian dysfunction to chemoresistance and propose actionable strategies-such as AKT inhibition or chronotherapy-to circumvent therapeutic failure. This work underscores the necessity of targeting circadian-metabolic crosstalk to improve outcomes in NSCLC.

Indexed as

ARNTL Transcription FactorsATP-Binding Cassette, Sub-Family C ProteinsCarcinoma, Non-Small-Cell LungCisplatinDrug Resistance, NeoplasmLactic AcidLung NeoplasmsAnimalsCell Line, TumorHumansSignal TransductionARNTL Transcription FactorsATP-Binding Cassette, Sub-Family C ProteinsBMAL1 protein, humanCisplatinLactic Acidmultidrug resistance-associated protein 1BMAL1cisplatin resistancelactateMRPNSCLC

Identifiers

PMID42029117
PMCPMC13108231

What OpenQuestion holds

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LicenceCC BY
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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.