Evidence map›Paper›PMID 36335371›Full record

ArticleJournal of translational medicine2022

Irradiation-induced exosomal HMGB1 to confer radioresistance via the PI3K/AKT/FOXO3A signaling pathway in ESCC.

Xingyu Du, Xueyuan Zhang, Jing Dong, Naiyi Zou, Dong Guo, Weinan Yao, Xiaobin Wang, Shuguang Li, Chunyang Song, Ke Yan and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 29 citations in OpenAlex.

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  12. Exosomes in esophageal cancer: function and therapeutic prospects.Medical oncology (Northwood, London, England) · 2024
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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 2 institutions in 1 country.

Xingyu DuDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Xueyuan ZhangDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Jing DongDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Naiyi ZouDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Dong GuoDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Weinan YaoDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Xiaobin WangDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Shuguang LiDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Chunyang SongDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Ke YanDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Wenbin ShenDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Shuchai ZhuDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China. 250969888@qq.com.
Fourth Hospital of Hebei Medical University · CNHebei Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRadioresistance is a major cause of treatment failure in esophageal squamous cell carcinoma (ESCC) radiotherapy, and the underlying mechanisms of radioresistance are still unclear. Irradiation (IR) stimulates changes in tumor-derived exosome contents, which can be taken up by recipient cells, playing an important role in the proliferation, cell cycle and apoptosis of recipient cells. This study investigated the effect of IR-induced exosomal high mobility group box 1 (HMGB1) on radioresistance in ESCC cells.

methodsPlasma exosomes were isolated from 21 ESCC patients and 24 healthy volunteers, and the expression of HMGB1 was examined. Then, the therapeutic effect of radiotherapy was analyzed according to the different expression levels of plasma exosomal HMGB1 in ESCC patients. The uptake of exosomes by recipient cells was verified by immunofluorescence staining, and the localization of exosomes and HMGB1 in cells before and after IR was evaluated. The effects of IR-induced exosomes on cell proliferation, invasion, apoptosis, cell cycle distribution and radioresistance after HMGB1 knockdown were verified. Moreover, western blotting was used to measure changes in the expression of cyclin B1, CDK1, Bax, Bcl2, phosphorylated histone H2AX and the PI3K/AKT/FOXO3A pathway in the HMGB1-knockdown exosome group and the negative control group.

resultsThe expression of HMGB1 in ESCC plasma exosomes was significantly increased compared with that in healthy volunteers, and high expression of HMGB1 in plasma exosomes was associated with radioresistance (P = 0.016). IR-induced the release of exosomal HMGB1 and promoted proliferation and radioresistance in recipient cells, with a sensitization enhancement ratio (SER) of 0.906 and 0.919, respectively. In addition, IR-induced exosomal HMGB1 promotes G2/M phase arrest by regulating the proteins cyclin B1 and CDK1, cooperating with the proteins Bax and Bcl2 to reduce the apoptosis rate through the PI3K/AKT/FOXO3A signaling pathway, and participated in IR-induced DNA damage repair through γH2AX.

conclusionThese findings indicate that high expression of plasma exosomal HMGB1 is associated with an adverse radiotherapy response. IR-induced exosomal HMGB1 enhances the radioresistance of ESCC cells.

Indexed as

Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaHMGB1 Proteinbcl-2-Associated X ProteinCell Line, TumorCell ProliferationCyclin B1HumansPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRadiation ToleranceSignal Transductionbcl-2-Associated X ProteinCyclin B1HMGB1 ProteinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktESCCExosomesHMGB1Radioresistance

Identifiers

PMID36335371
PMCPMC9636677
OpenAlexW4308303094

What OpenQuestion holds

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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.