Evidence map›Paper›PMID 35395767›Full record

ArticleMolecular cancer2022

The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKKε/TBK1/IRF3 pathway in head and neck squamous cell carcinoma.

Shufang Jin, Mingyu Li, Hanyue Chang, Ruijie Wang, Zhiyuan Zhang, Jianjun Zhang, Yue He, Hailong Ma

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

Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
10.1field-weighted citation impact, top 1% 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

83 citing papers in PubMed, 120 citations in OpenAlex.

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  2. Targeting mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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23 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

Shufang Jin *Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China.
Mingyu Li *Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China.
Hanyue ChangDepartment of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China.
Ruijie WangDepartment of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China.
Zhiyuan ZhangDepartment of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China.
Jianjun ZhangDepartment of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China. zjjshuobo@163.com.
Yue HeDepartment of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China. william5218@126.com.
Hailong MaDepartment of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 639, Zhizaoju Rd, Shanghai, 200011, China. mahl21@sjtu.edu.cn.ORCID 0000-0003-4110-1417
Shanghai Jiao Tong University · CNNational Clinical Research Center for Digestive Diseases · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundN6-methyladenosine (m6A) RNA modification plays a critical role in various physiological and pathological conditions. However, the role of m6A modification in head and neck squamous cell carcinoma (HNSCC) remains elusive.

methodsIn this study, the expression of m6A demethylases was detected by HNSCC tissue microarray. m6A-RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were used to identify downstream targets of ALKBH5. Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) was used to explore the m6A "readers". Tumor-infiltrating lymphocytes were analyzed in SCC7-bearing xenografts in C3H mice.

resultsHere, we demonstrate the downregulation of m6A status and upregulation of two demethylases in HNSCC. Silencing the m6A demethylase alkB homolog 5, RNA demethylase (ALKBH5) suppresses tumor progression in vitro and in vivo. m6A-RNA immunoprecipitation sequencing reveals that ALKBH5 downregulates the m6A modification of DDX58 mRNA. Moreover, RIG-I, encoded by the DDX58 mRNA, reverses the protumorigenic characteristics of ALKBH5. ChIRP-MS demonstrates that HNRNPC binds to the m6A sites of DDX58 mRNA to promote its maturation. ALKBH5 overexpression inhibits RIG-I-mediated IFNα secretion through the IKKε/TBK1/IRF3 pathway. The number of tumor-infiltrating lymphocytes in C3H immunocompetent mice is reduced by ALKBH5 overexpression and restored by IFNα administration. Upregulation of AKLBH5 negatively correlates with RIG-I and IFNα expression in HNSCC patients.

conclusionsThese findings unveil a novel mechanism of immune microenvironment regulation mediated by m6A modification through the ALKBH5/RIG-I/IFNα axis, providing a rationale for therapeutically targeting epitranscriptomic modulators in HNSCC.

Indexed as

AlkB Homolog 5, RNA DemethylaseHead and Neck NeoplasmsI-kappa B KinaseSquamous Cell Carcinoma of Head and NeckAnimalsDEAD Box Protein 58HumansInterferon-alphaInterferon Regulatory Factor-3MiceMice, Inbred C3HProtein Serine-Threonine KinasesRNA, MessengerTumor MicroenvironmentALKBH5 protein, humanAlkB Homolog 5, RNA DemethylaseDEAD Box Protein 58I-kappa B KinaseInterferon-alphaInterferon Regulatory Factor-3IRF3 protein, humanProtein Serine-Threonine KinasesRNA, MessengerTBK1 protein, humanALKBH5Head and neck squamous cell carcinomaInterferon alphaN6-methyladenosineRIG-I

Identifiers

PMID35395767
PMCPMC8994291
OpenAlexW4223527358

What OpenQuestion holds

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LicenceCC BY
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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.