Evidence map›Paper›PMID 35176309›Full record

ArticleGastroenterology2022

Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2-AKT-TGF-β Signaling Axis in Pancreatic Cancer.

Xiuhui Shi, Jingxuan Yang, Mingyang Liu, Yuqing Zhang, Zhijun Zhou, Wenyi Luo, Kar-Ming Fung, Chao Xu, Michael S Bronze, Courtney W Houchen and 1 more

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

Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
11.5field-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

81 citing papers in PubMed, 139 citations in OpenAlex.

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  14. Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026
    Review
  15. Review
  16. Article
  17. Article
  18. Metal-related cell death and its application in pancreatic cancer.Expert reviews in molecular medicine · 2025
    Review
  19. Article
  20. Article

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

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

11 authors at 1 institution in 1 country.

Xiuhui ShiDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Jingxuan YangDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Mingyang LiuDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Yuqing ZhangDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Zhijun ZhouDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Wenyi LuoDepartment of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Kar-Ming FungDepartment of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Chao XuDepartment of Biostatistics and Epidemiology, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Michael S BronzeDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Courtney W HouchenDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Min LiDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Electronic address: Min-Li@ouhsc.edu.
University of Oklahoma Health Sciences Center · US

Funding

Tissue Pathology Shared ResourceP30CA225520 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ROBERT S. MANNEL · 2018 to 2026
$27.1M
NCI NIH HHS P30 CA225520
6 · The paper itself

Abstract

BACKGROUND &

aimsPancreatic cancer has the highest prevalence of cancer-associated cachexia among all cancers. ZIP4 promotes pancreatic cancer progression by regulating oncogenic miR-373, and perturbation of circular RNAs (circRNAs) is associated with cancer aggressiveness. This study aimed to identify circRNAs involved in ZIP4/miR-373-driven cancer growth and cachexia and decipher the underlying mechanism.

methodsDifferentially expressed circRNAs and potential targets of microRNA were identified through in silico analysis. The RNA interactions were determined by means of biotinylated microRNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. The function of circRNA in ZIP4-miR-373 signaling axis were examined in human pancreatic cancer cells, 3-dimensional spheroids and organoids, mouse models, and clinical specimens. Mouse skeletal muscles were analyzed by means of histology.

resultsWe identified circANAPC7 as a sponge for miR-373, which inhibited tumor growth and muscle wasting in vitro and in vivo. Mechanistic studies showed that PHLPP2 is a downstream target of ZIP4/miR-373. CircANAPC7 functions through PHLPP2-mediated dephosphorylation of AKT, thus suppressing cancer cell proliferation by down-regulating cyclin D1 and inhibiting muscle wasting via decreasing the secretion of transforming growth factor-β through STAT5. We further demonstrated that PHLPP2 induced dephosphorylation of CREB, a zinc-dependent transcription factor activated by ZIP4, thereby forming a CREB-miR-373-PHLPP2 feed-forward loop to regulate tumor progression and cancer cachexia.

conclusionThis study identified circANAPC7 as a novel tumor suppressor, which functions through the CREB-miR-373-PHLPP2 axis, leading to AKT dephosphorylation, and cyclin D1 and transforming growth factor-β down-regulation to suppress tumor growth and muscle wasting in pancreatic cancer.

Indexed as

CachexiaMicroRNAsPancreatic NeoplasmsPhosphoprotein PhosphatasesProto-Oncogene Proteins c-aktRNA, CircularTransforming Growth Factor betaAnimalsCell Line, TumorCell ProliferationCyclin D1HumansMiceMusclesCcnd1 protein, mouseCyclin D1MicroRNAsPHLPP2 protein, humanPHLPP2 protein, mousePhosphoprotein PhosphatasesProto-Oncogene Proteins c-aktRNA, CircularTransforming Growth Factor betaCachexiaCircRNAMicroRNAProliferation

Identifiers

PMID35176309
PMCPMC10428768
OpenAlexW4213018448

What Socratic holds

Textmetadata
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 Socratic graph.