Evidence map›Paper›PMID 37391589›Full record

ArticleJournal of gastroenterology2023

VIRMA facilitates intrahepatic cholangiocarcinoma progression through epigenetic augmentation of TMED2 and PARD3B mRNA stabilization.

Hongfa Xu, Xiaowen Lin, Zhongliang Li, Xu He, Yong Li, Lige Qiu, Ligong Lu, Bing Liu, Meixiao Zhan, Ke He

Abstract read
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In one paragraph

Article in Journal of gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. mFrontiers in cell and developmental biology · 2026
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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

10 authors at 3 institutions in 1 country.

Hongfa Xu *Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Xiaowen Lin *Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Zhongliang Li *Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Xu HeGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Yong LiGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Lige QiuGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Ligong LuGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Bing LiuGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China.
Meixiao ZhanGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, 519000, Guangdong, China. zhanmeixiao1987@126.com.
Ke HeMinimally Invasive Tumor Therapies Center, Guangdong Second Provincial General Hospital, Guangzhou, 510310, Guangdong, China. hiker00006@126.com.
Zhuhai People's Hospital · CNJinan University · CNGuangdong Provincial People's Hospital · CN

Funding

Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment 2021B1212040004National Natural Science Foundation of China 82230067National Natural Science Foundation of China 82272103Scientific Research Foundation of Guangdong Medical University of China 2021093728Scientific Research Foundation of Guangdong Medical University of China 2021113808the Natural Science Foundation of Guangdong Province of China 2022B1515020010
6 · The paper itself

Abstract

backgroundN6-methyladenine modification of RNA, a critical component of the regulatory role at the post-transcriptional level, has a crucial effect on tumor development and progression. vir-Like m6A methyltransferase associated (VIRMA) has been recently discovered as an N6-methyladenine methyltransferase; however, its specific role in intrahepatic cholangiocarcinoma (ICC) remains to be investigated in-depth.

methodsVIRMA expression and its association with clinicopathological characteristics were evaluated using The Cancer Genome Atlas (TCGA) dataset and tissue microarrays. In vivo and in vitro assays were performed to determine the role of VIRMA in ICC proliferation and metastasis. The underlying mechanism by which VIRMA influences ICC was clarified by RNA sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), SLAM sequencing (SLAM-seq), RNA immunoprecipitation, a luciferase reporter assay, and chromatin immunoprecipitation assay.

resultsVIRMA showed high expression in ICC tissues, and this finding predicted a dismal prognostic outcome. The high expression of VIRMA in ICC was due to the demethylation of H3K27me3 modification in the promoter region. Functionally, VIRMA is required for the endothelial-mesenchymal transition (EMT) process in ICC cells, as shown by multiple ICC models in in vitro and in vivo experiments. Mechanistically, multi-omics analysis using ICC cells demonstrated that TMED2 and PARD3B were the direct downstream target of VIRMA. The methylated TMED2 and PARD3B transcripts were directly recognized by HuR, which exerted stabilizing effects on its bound RNA. VIRMA-induced expression of TMED2 and PARD3B activated the Akt/GSK/β-catenin and MEK/ERK/Slug signaling pathways, thereby promoting ICC proliferation and metastasis.

conclusionsThe present study showed that VIRMA plays a critical role in ICC development by stabilizing TMED2 and PARD3B expression through the m6A-HuR-mediated mechanism. Thus, demonstrating VIRMA and its pathway as candidate therapeutic targets for ICC treatment.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaRNA-Binding ProteinsBile Ducts, IntrahepaticCarrier ProteinsCell Line, TumorEpigenesis, GeneticHumansMembrane ProteinsMethyltransferasesRNA, MessengerVesicular Transport ProteinsCarrier ProteinsMembrane ProteinsMethyltransferasesPARD3B protein, humanRNA-Binding ProteinsRNA, MessengerTMED2 protein, humanVesicular Transport ProteinsVIRMA protein, humanICCN6-methyladenosinePARD3BTMED2VIRMA

Identifiers

PMID37391589
OpenAlexW4382677615

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.