Evidence map›Paper›PMID 37532176›Full record

ArticleMolecular & cellular proteomics : MCP2023

The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.

Miao Gao, Heng Xiao, Yonglan Liang, Huimin Cai, Xiaojing Guo, Jianwei Lin, Suling Zhuang, Jianhua Xu, Shengnan Ye

Abstract read
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In one paragraph

Article in Molecular & cellular proteomics : MCP, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 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

9 authors.

Miao GaoDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Heng XiaoDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Yonglan LiangDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Huimin CaiDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Xiaojing GuoDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Jianwei LinDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Suling ZhuangDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Jianhua XuDepartment of Pharmacology, School of Pharmacy, Fujian Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, China. Electronic address: xjh@fjmu.edu.cn.
Shengnan YeDepartment of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. Electronic address: yeshengnan63@fjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholesteatoma is a chronic inflammatory ear disease with abnormal keratinized epithelium proliferation and tissue damage. However, the mechanism of keratinized epithelium hyperproliferation in cholesteatoma remains unknown. Hence, our study sought to shed light on mechanisms affecting the pathology and development of cholesteatoma, which could help develop adjunctive treatments. To investigate molecular changes in cholesteatoma pathogenesis, we analyzed clinical cholesteatoma specimens and paired ear canal skin with mass spectrometry-based proteomics and bioinformatics. From our screen, alpha-synuclein (SNCA) was overexpressed in middle ear cholesteatoma and might be a key hub protein associated with inflammation, proliferation, and autophagy in cholesteatoma. SNCA was more sensitive to lipopolysaccharide-induced inflammation, and autophagy marker increase was accompanied by autophagy activation in middle ear cholesteatoma tissues. Overexpression of SNCA activated autophagy and promoted cell proliferation and migration, especially under lipopolysaccharide inflammatory stimulation. Moreover, inhibiting autophagy impaired SNCA-mediated keratinocyte proliferation and corresponded with inhibition of the PI3K/AKT/CyclinD1 pathways. Also, 740Y-P, a PI3K activator reversed the suppression of autophagy and PI3K signaling by siATG5 in SNCA-overexpressing cells, which restored proliferative activity. Besides, knockdown of SNCA in RHEK-1 and HaCaT cells or knockdown of PI3K in RHEK-1 and HaCaT cells overexpressing SNCA both resulted in attenuated cell proliferation. Our studies indicated that SNCA overexpression in cholesteatoma might maintain the proliferative ability of cholesteatoma keratinocytes by promoting autophagy under inflammatory conditions. This suggests that dual inhibition of SNCA and autophagy may be a promising new target for treating cholesteatoma.

Indexed as

Cholesteatoma, Middle Earalpha-SynucleinAutophagyCell ProliferationHumansInflammationLipopolysaccharidesPhosphatidylinositol 3-KinasesProteomicsProto-Oncogene Proteins c-aktSignal Transductionalpha-SynucleinLipopolysaccharidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSNCA protein, humanalpha-synucleinautophagycholesteatomaproliferationproteomics

Identifiers

PMID37532176
PMCPMC10495652

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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.