Evidence map›Paper›PMID 31088485›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

Long non-coding RNA AGAP2-AS1, functioning as a competitive endogenous RNA, upregulates ANXA11 expression by sponging miR-16-5p and promotes proliferation and metastasis in hepatocellular carcinoma.

Zhikui Liu, Yufeng Wang, Liang Wang, Bowen Yao, Liankang Sun, Runkun Liu, Tianxiang Chen, Yongshen Niu, Kangsheng Tu, Qingguang Liu

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. 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 It has been retracted, and should not be counted.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 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
9.5field-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

72 citing papers in PubMed, 149 citations in OpenAlex.

  1. The mechanism of ncRNA in trastuzumab resistance in HER2-positive tumors.Medical oncology (Northwood, London, England) · 2025
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  13. The Role of Long Noncoding RNA (lncRNAs) Biomarkers in Renal Cell Carcinoma.International journal of molecular sciences · 2022
    Review
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  20. Review

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Zhikui LiuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Yufeng WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Liang WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Bowen YaoDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Liankang SunDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Runkun LiuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Tianxiang ChenDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Yongshen NiuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Kangsheng TuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Qingguang LiuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China. liuqingguang@vip.sina.com.
First Affiliated Hospital of Xi'an Jiaotong University · CN

Funding

National Natural Science Foundation of China 81402039National Natural Science Foundation of China 81572847
6 · The paper itself

Abstract

backgroundAccumulating evidence has highlighted the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of hepatocellular carcinoma (HCC). Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA-AGAP2-AS1 on the biological behaviors of HCC.

methodsEdU, Transwell and flow cytometry were used to determine proliferation, migration, invasion and apoptosis of HCC cells in vitro. The subcutaneous tumor model and lung metastasis mouse model in nude mice was established to detect tumor growth and metastasis of HCC in vivo. The direct binding of miR-16-5p to 3'UTR of ANXA11 was confirmed by luciferase reporter assay. The expression of AGAP2-AS1 and miR-16-5p in HCC specimens and cell lines were detected by real-time PCR. The correlation among AGAP2-AS1 and miR-16-5p were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay.

resultsHere, we demonstrated that AGAP2-AS1 expression was up-regulated in HCC tissues and cell lines, especially in metastatic and recurrent cases. Gain- and loss-of-function experiments indicated that AGAP2-AS1 promoted cell proliferation, migration, invasion, EMT progression and inhibited apoptosis of HCC cells in vitro and in vivo. Further studies demonstrated that AGAP2-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-16-5p in HCC cells. Functionally, gain- and loss-of-function studies showed that miR-16-5p promoted HCC progression and alteration of miR-16-5p abolished the promotive effects of AGAP2-AS1 on HCC cells. Moreover, ANXA11 was identified as direct downstream targets of miR-16-5p in HCC cells, and mediated the functional effects of miR-16-5p and AGAP2-AS1 in HCC, resulting in AKT signaling activation. Clinically, AGAP2-AS1 and miR-16-5p expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the overexpression of AGAP2-AS1 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by AGAP2-AS1 knockdown.

conclusionsTaken together, this research supports the first evidence that AGAP2-AS1 plays an oncogenic role in HCC via AGAP2-AS1/miR-16-5p/ANXA11/AKT axis pathway and represents a promising therapeutic strategy for HCC patients.

Indexed as

Gene Expression Regulation, NeoplasticRNA Interference3' Untranslated RegionsAgedAged, 80 and overAnimalsAnnexinsBiomarkers, TumorCarcinoma, HepatocellularCell Line, TumorCell MovementCell ProliferationDisease Models, AnimalDisease ProgressionEpithelial-Mesenchymal TransitionFemale3' Untranslated RegionsAnnexinsBiomarkers, Tumorlong non-coding RNA AGAP2-AS1, humanMicroRNAsMIRN16 microRNA, humanProto-Oncogene Proteins c-aktRNA, Long NoncodingAGAP2-AS1ANXA11Hepatocellular carcinomamiR-16-5pProliferation

Identifiers

PMID31088485
PMCPMC6518827
OpenAlexW2947173581

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.