Evidence map›Paper›PMID 37063434›Full record

ArticleInternational journal of biological sciences2023

PI3K/ c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism.

Chenming Ni, Wenyu Liu, Kailian Zheng, Shiwei Guo, Bin Song, Wei Jing, Gang Li, Bo Li, Canrong Ni, Keqing Shi and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

12 authors at 4 institutions in 1 country.

Chenming NiDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Wenyu LiuDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Kailian ZhengDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Shiwei GuoDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Bin SongDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Wei JingDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Gang LiDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Bo LiDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Canrong NiDepartment of Pathology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Keqing ShiPrecision Medical Center Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, 325000, China.
Gang JinDepartment of Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Guanzhen YuPrecision Medical Center Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, 325000, China.
Changhai Hospital · CNSecond Military Medical University · CNFirst Affiliated Hospital of Wenzhou Medical University · CNWenzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MLL-AFF4 fusion gene has been discovered in acute leukemia, whether AFF4 alone plays a role in tumor, especially pancreatic tumorigenesis, is still elusive. Increasing evidence suggests that cancer cells altered nucleotide metabolism during tumorigenesis. In present study, we observed AFF4 overexpression promoted cell proliferation, colony formation and cell cycle progression while loss of AFF4 impairs above phenotypes of pancreatic ductal carcinoma (PDAC) cells. Using RNA-profiling, we revealed that HPRT1 and IMPDH2, two enzymes in the nucleotide metabolism pathway, were upregulated following AFF4 overexpression. Simultaneous expression of HPRT1 and IMPDH2 would mainly rescue the phenotypes of cells lacking AFF4. Additionally, xenograft study proved HPRT1 and IMPDH2 genetically function in the downstream of AFF4, which was recruited by PAX2 when CDK9 mediated AFF4 phosphorylation at S388 and drove HPRT1 and IMPDH2 expression. We further discovered PI3K/c-Myc axis is required for AFF4 expression in PDAC cells. Finally, we obtained the positive correlation between c-Myc and AFF4 or AFF4 and HPRT1/IMPDH2 in clinical PDAC samples. Otherwise, we conducted data-mining and found that the expression levels of AFF4 and HPRT1/IMPDH2 are correlated with patients' prognosis, establishing AFF4 as a potential biomarker and therapeutic target for PDAC.

Indexed as

Carcinoma, Pancreatic DuctalPancreatic NeoplasmsCarcinogenesisCell Line, TumorCell MovementCell ProliferationCell Transformation, NeoplasticGene Expression Regulation, NeoplasticHumansNucleotidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-mycTranscriptional Elongation FactorsAFF4 protein, humanNucleotidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-mycTranscriptional Elongation FactorsAFF4c-MycNucleotide metabolismPancreatic cancerPI3K

Identifiers

PMID37063434
PMCPMC10092763
OpenAlexW4364323087

What OpenQuestion holds

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LicenceCC BY
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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.