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Molecular Cancer
Published in: Molecular Cancer 1/2024

Open Access 01-12-2024 | Pancreatic Cancer | Research

Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4–HDAC4–RUNX2–GAMT-mediated apoptosis

Authors: Hao Yuan, Chuang Chen, Haonan Li, Gexi Qu, Luyao Chen, Yaxing Liu, Yufeng Zhang, Qiang Zhao, Changhong Lian, Aifang Ji, Xuedong Hou, Xinjian Liu, Kuirong Jiang, Yi Zhu, Yuan He

Published in: Molecular Cancer | Issue 1/2024

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Abstract

Background

Pancreatic cancer (PC) is an extremely malignant tumor with low survival rate. Effective biomarkers and therapeutic targets for PC are lacking. The roles of circular RNAs (circRNAs) in cancers have been explored in various studies, however more work is needed to understand the functional roles of specific circRNAs. In this study, we explore the specific role and mechanism of circ_0035435 (termed circCGNL1) in PC.

Methods

qRT-PCR analysis was performed to detect circCGNL1 expression, indicating circCGNL1 had low expression in PC cells and tissues. The function of circCGNL1 in PC progression was examined both in vitro and in vivo. circCGNL1-interacting proteins were identified by performing RNA pulldown, co-immunoprecipitation, GST-pulldown, and dual-luciferase reporter assays.

Results

Overexpressing circCGNL1 inhibited PC proliferation via promoting apoptosis. CircCGNL1 interacted with phosphatase nudix hydrolase 4 (NUDT4) to promote histone deacetylase 4 (HDAC4) dephosphorylation and subsequent HDAC4 nuclear translocation. Intranuclear HDAC4 mediated RUNX Family Transcription Factor 2 (RUNX2) deacetylation and thereby accelerating RUNX2 degradation. The transcription factor, RUNX2, inhibited guanidinoacetate N-methyltransferase (GAMT) expression. GAMT was further verified to induce PC cell apoptosis via AMPK–AKT–Bad signaling pathway.

Conclusions

We discovered that circCGNL1 can interact with NUDT4 to enhance NUDT4-dependent HDAC4 dephosphorylation, subsequently activating HDAC4–RUNX2–GAMT-mediated apoptosis to suppress PC cell growth. These findings suggest new therapeutic targets for PC.
Appendix
Available only for authorised users
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Metadata
Title
Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4–HDAC4–RUNX2–GAMT-mediated apoptosis
Authors
Hao Yuan
Chuang Chen
Haonan Li
Gexi Qu
Luyao Chen
Yaxing Liu
Yufeng Zhang
Qiang Zhao
Changhong Lian
Aifang Ji
Xuedong Hou
Xinjian Liu
Kuirong Jiang
Yi Zhu
Yuan He
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2024
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-023-01923-7

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