Evidence map›Paper›PMID 31279780›Full record

ArticleEBioMedicine2019

PLAGL2 and POFUT1 are regulated by an evolutionarily conserved bidirectional promoter and are collaboratively involved in colorectal cancer by maintaining stemness.

Daojiang Li, Changwei Lin, Nanpeng Li, Yuheng Du, Chunxing Yang, Yang Bai, Zhicai Feng, Chen Su, Runliu Wu, Shenglei Song and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 51 citations in OpenAlex.

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  11. Preliminary study on the mechanism of POFUT1 in colorectal cancer.Medical oncology (Northwood, London, England) · 2023
    Article
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  16. The NMolecular cancer · 2022
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  20. Unexplored regulatory sequences of divergently pairedExperimental and therapeutic medicine · 2021
    Article
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

16 authors at 2 institutions in 2 countries.

Daojiang LiDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China; Department of Colorectal and Anal Surgery of Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China.
Changwei LinDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Nanpeng LiDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Yuheng DuDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Chunxing YangDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Yang BaiDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Zhicai FengDepartment of Burns and Plastic Surgery, the 3rd Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Chen SuDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Runliu WuDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Shenglei SongDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Peicheng YanDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Miao ChenDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Arad JainCollege of Arts and Science, University of Virginia, Charlottesville, Virginia 22904, United States of America.
Lihua HuangCenter for Experimental Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Yi ZhangDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China.
Xiaorong LiDepartment of gastroenterological surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China; Center for Experimental Medicine, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, China. Electronic address: xiaorongli@csu.edu.cn.
Central South University · CNUniversity of Virginia · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOur previous study revealed that PLAGL2 or POFUT1 can promote tumorigenesis and maintain significant positive correlations in colorectal cancer (CRC). However, the mechanism leading to the co-expression and the underlying functional and biological implications remain unclear.

methodsClinical tumor tissues and TCGA dataset were utilized to analyze the co-expression of PLAGL2 and POFUT1. Luciferase reporter assays, specially made bidirectional promoter vectors and ectopic expression of 3'UTR were employed to study the mechanisms of co-expression. In vitro and in vivo assays were performed to further confirm the oncogenic function of both. The sphere formation assay, immunofluorescence, Western blot and qRT-PCR were performed to investigate the effect of both genes in colorectal cancer stem cells (CSCs).

findingsPLAGL2 and POFUT1 maintained co-expression in CRC (r = 0.91, p < .0001). An evolutionarily conserved bidirectional promoter, rather than post-transcriptional regulation by competing endogenous RNAs, caused the co-expression of PLAGL2 and POFUT1 in CRC. The bidirectional gene pair PLAGL2/POFUT1 was subverted in CRC and acted synergistically to promote colorectal tumorigenesis by maintaining stemness of colorectal cancer stem cells through the Wnt and Notch pathways. Finally, PLAGL2 and POFUT1 share transcription factor binding sites, and introducing mutations into promoter regions with shared transcription regulatory elements led to a decrease in the PLAGL2/POFUT1 promoter activity in both directions.

interpretationOur team identified for the first time a bidirectional promoter pair oncogene, PLAGL2-POFUT1, in CRC. The two genes synergistically promote the progression of CRC and affect the characteristics of CSCs, which can offer promising intervention targets for clinicians and researchers. FUND: National Nature Science Foundation of China, the Hunan province projects of Postgraduate Independent Exploration and Innovation of Central South University.

Indexed as

3' Untranslated RegionsAnimalsCarcinogenesisCell Line, TumorCell ProliferationColorectal NeoplasmsDNA-Binding ProteinsFucosyltransferasesGene Expression Regulation, NeoplasticHumansMiceNeoplastic Stem CellsPromoter Regions, GeneticRNA-Binding ProteinsTranscription FactorsXenograft Model Antitumor Assays3' Untranslated RegionsDNA-Binding ProteinsFucosyltransferasesPLAGL2 protein, humanpolypeptide fucosyltransferaseRNA-Binding ProteinsTranscription FactorsBidirectional promoterCancer stem cellCo-expressionColorectal cancerPLAGL2POFUT1

Identifiers

PMID31279780
PMCPMC6642334
OpenAlexW2955336689

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.