Evidence map›Paper›PMID 36153596›Full record

ArticleCell communication and signaling : CCS2022

Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3.

Tianyi Shen, Suqin Miao, Yulin Zhou, Xiaoming Yi, Song Xue, Bowen Du, Chaopeng Tang, Le Qu, Dian Fu, Ruipeng Jia and 1 more

Open access · goldAbstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

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  8. Roles of LncRNA ARSR in tumor proliferation, drug resistance, and lipid and cholesterol metabolism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
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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 2 institutions in 1 country.

Tianyi Shen *Department of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Suqin Miao *Department of Anesthesiology, Jinling Hospital, Nanjing University Medical School, Nanjing, 210002, Jiangsu, China.
Yulin Zhou *Department of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Xiaoming YiDepartment of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Song XueDepartment of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Bowen DuDepartment of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Chaopeng TangDepartment of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Le QuDepartment of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Dian FuDepartment of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.
Ruipeng JiaDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210002, Jiangsu, China. ruipengj@163.com.
Haowei HeDepartment of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, 210002, Jiangsu, China. hohowell@gmail.com.ORCID 0000-0002-0358-4983
Nanjing General Hospital of Nanjing Military Command · CNNanjing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear.

methodsMacrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation.

resultsThe ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-β) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-β and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo.

conclusionExosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract.

Indexed as

Carcinoma, Renal CellExosomesKidney NeoplasmsMicroRNAsRNA, Long NoncodingAnimalsCell Line, TumorHumansInterleukin-10Macrophage ActivationMacrophagesMiceNF-kappa BRNA, MessengerSTAT3 Transcription FactorTransforming Growth Factor betaInterleukin-10MicroRNAsNF-kappa BRNA, Long NoncodingRNA, MessengerSTAT3 protein, humanSTAT3 Transcription FactorTransforming Growth Factor betaTransforming Growth FactorsClear cell renal cell carcinomaExosomeslncRNA AP000439.2MacrophageNF-κB signaling pathwaySTAT3

Identifiers

PMID36153596
PMCPMC9509597
OpenAlexW4296954426

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.