Evidence map›Paper›PMID 32020881›Full record

ArticleMolecular cancer2020

Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation.

Mingli Han, Yuanting Gu, Pengwei Lu, Jingyi Li, Hui Cao, Xiangke Li, Xueke Qian, Chao Yu, Yunqing Yang, Xue Yang and 4 more

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Molecular cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 114 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 2 pooled it
14.0field-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

114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 191 citations in OpenAlex.

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  15. Qingrexiaoji Recipe Regulates the Differentiation of M2 TAMCombinatorial chemistry & high throughput screening · 2024
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54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Mingli HanDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. minglihan@126.com.
Yuanting GuDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Pengwei LuDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Jingyi LiDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Hui CaoDepartment of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Xiangke LiDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Xueke QianDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Chao YuDepartment of General Surgery, University-Town Hospital of Chongqing Medical University, Chongqing, 400016, China.
Yunqing YangDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Xue YangDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Na HanDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Dongwei DouDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Jianguo HuDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Huaying DongDepartment of General Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No.19 XiuHua Road, Xiuying District, Haikou, 570311, China. dr_dhy@163.com.ORCID 0000-0002-4905-6940
First Affiliated Hospital of Zhengzhou University · CNChongqing Medical University · CNDalian Medical University · CNHainan General Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer.

methodsLncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance.

resultsAFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level.

conclusionExosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

Indexed as

Drug Resistance, NeoplasmAnimalsAntineoplastic Agents, ImmunologicalApoptosisBiomarkers, TumorBreast NeoplasmsCell ProliferationErb-b2 Receptor Tyrosine KinasesExosomesFemaleGene Expression Regulation, NeoplasticHeterogeneous Nuclear Ribonucleoprotein D0HumansMiceMice, Inbred BALB CMice, NudeAFAP1-AS1 long noncoding RNA, humanAntineoplastic Agents, ImmunologicalBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesHeterogeneous Nuclear Ribonucleoprotein D0HNRNPD protein, humanRNA, Long NoncodingTrastuzumabAFAP1-AS1Breast cancerERBB2ExosomeTrastuzumab resistance

Identifiers

PMID32020881
PMCPMC7001272
OpenAlexW3010445736

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.