Evidence map›Paper›PMID 35773668›Full record

ArticleBMC medicine2022

A novel CREB5/TOP1MT axis confers cisplatin resistance through inhibiting mitochondrial apoptosis in head and neck squamous cell carcinoma.

Tong Tong, Xing Qin, Yingying Jiang, Haiyan Guo, Xiaoning Wang, Yan Li, Fei Xie, Hao Lu, Peisong Zhai, Hailong Ma and 1 more

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

Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 31 citations in OpenAlex.

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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

11 authors at 5 institutions in 2 countries.

Tong Tong *Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Rd, Shanghai, 200011, People's Republic of China.
Xing Qin *Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Rd, Shanghai, 200011, People's Republic of China.
Yingying JiangDepartment of Dentistry, Affiliated Hospital of Weifang Medical University, Weifang, 261000, People's Republic of China.
Haiyan GuoDepartment of Clinical Laboratory, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.
Xiaoning WangDepartment of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.
Yan LiShanghai Institute of Immunology Center for Microbiota & Immune Related Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China.
Fei XieDepartment of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Rd, Shanghai, 200011, People's Republic of China.
Hao LuDepartment of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Rd, Shanghai, 200011, People's Republic of China.
Peisong ZhaiDepartment of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Rd, Shanghai, 200011, People's Republic of China.
Hailong MaDepartment of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Rd, Shanghai, 200011, People's Republic of China. mahl21@sjtu.edu.cn.
Jianjun ZhangDepartment of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Rd, Shanghai, 200011, People's Republic of China. zjjbio@sjtu.edu.cn.
Shanghai Ninth People's Hospital · CNShanghai Jiao Tong University · CNNational Clinical Research · USShanghai First People's Hospital · CNWeifang Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCisplatin resistance is one of the main causes of treatment failure and death in head and neck squamous cell carcinoma (HNSCC). A more comprehensive understanding of the cisplatin resistance mechanism and the development of effective treatment strategies are urgent.

methodsRNA sequencing, RT-PCR, and immunoblotting were used to identify differentially expressed genes associated with cisplatin resistance. Gain- and loss-of-function experiments were performed to detect the effect of CREB5 on cisplatin resistance and mitochondrial apoptosis in HNSCC. Chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay, and immunoblotting experiments were performed to explore the underlying mechanisms of CREB5.

resultsCREB5 was significantly upregulated in cisplatin-resistant HNSCC (CR-HNSCC) patients, which was correlated with poor prognosis. CREB5 overexpression strikingly facilitated the cisplatin resistance of HNSCC cells in vitro and in vivo, while CREB5 knockdown enhanced cisplatin sensitivity in CR-HNSCC cells. Interestingly, the activation of AKT signaling induced by cisplatin promoted nucleus translocation of CREB5 in CR-HNSCC cells. Furthermore, CREB5 transcriptionally activated TOP1MT expression depending on the canonical motif. Moreover, CREB5 silencing could trigger mitochondrial apoptosis and overcome cisplatin resistance in CR-HNSCC cells, which could be reversed by TOP1MT overexpression. Additionally, double-targeting of CREB5 and TOP1MT could combat cisplatin resistance of HNSCC in vivo.

conclusionsOur findings reveal a novel CREB5/TOP1MT axis conferring cisplatin resistance in HNSCC, which provides a new basis to develop effective strategies for overcoming cisplatin resistance.

Indexed as

Antineoplastic AgentsCisplatinCyclic AMP Response Element-Binding Protein ADNA Topoisomerases, Type IHead and Neck NeoplasmsSquamous Cell Carcinoma of Head and NeckApoptosisCell Line, TumorDrug Resistance, NeoplasmHumansMitochondriaSignal TransductionAntineoplastic AgentsCisplatinCREB5 protein, humanCyclic AMP Response Element-Binding Protein ADNA Topoisomerases, Type ITOP1MT protein, humanCisplatin resistanceCREB5HNSCCMitochondrial apoptosisTOP1MT

Identifiers

PMID35773668
PMCPMC9248137
OpenAlexW4283744497

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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.