WTAP/IGF2BP3-mediated GBE1 expression accelerates the proliferation and enhances stemness in pancreatic cancer cells via upregulating c-Myc

Sep 22, 2026

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The brief report investigates how WTAP/IGF2BP3-mediated N6-methyladenosine (m6A) modification regulates Glucan Branching Enzyme 1 (GBE1) and drives pancreatic cancer malignancy. Background links pancreatic cancer aggressiveness and poor prognosis to dysregulated m6A and GBE1 biology. Clinical and cellular validation show GBE1 upregulation correlates with worse outcomes, promotes proliferation and stemness-like traits, and knockdown attenuates malignancy. Mechanistically, WTAP and IGF2BP3 increase GBE1 mRNA stability and expression, activating a c-Myc-dependent pathway supporting rescue experiments, highlighting therapeutic potential.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Background

Methods

Results

Conclusions

Jin et al. Cellular & Molecular Biology Letters (2024) 29:97 [https://doi.org/10.1](https://doi.org/10.1) 186/s11658‑024‑00611‑8 Cellular & Molecular Biology Letters BRIEF REPORT Open Access WTAP/IGF2BP3‑mediated GBE1 expression accelerates the proliferation and enhances stemness in pancreatic cancer cells via upregulating c‑Myc Weiwei Jin1,2†, Yanru Yao3†, Yuhan Fu3†, Xiangxiang Lei3, Wen Fu4, Qiliang Lu4, Xiangmin Tong1, Qiuran Xu1*, Wei Su5,6* and Xiaoge Hu1* | †Weiwei Jin, Yanru Yao andYuhan Fu contribute equally to this study. | | --- | | *Correspondence:
[xuqiuran@hmc.edu.cn](xuqiuran@hmc.edu.cn); [sagowei@outlook.com](sagowei@outlook.com); [huxiaoge2008xmu@163.com](huxiaoge2008xmu@163.com) | 1 Zhejiang Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China 2 General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China 3 Hangzhou Medical College, Hangzhou, China 4 The Medical College of Qingdao University, Qingdao, China 5 Department of Hepatobiliaryand Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 6 Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China Abstract Background: Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism. However, the function of GBE1 and Whether GBE1 occurs m6A modification in PC progression remains to be illustrated. Methods: The clinical prognosis of GBE1 was analyzed through online platform. The expression of GBE1 was obtained from online platform and then verified in normal and PC cell lines. Lentivirus was used to generated GBE1 stable-overexpression or knockdown PC cells. Cell Counting Kit (CCK-8), colony formation assay, sphere formation assay and flow cytometry assay were conducted to analyze cell proliferation and stemness ability in vitro. Subcutaneous and orthotopic mouse models were used to verify the function of GBE1 in vivo. RNA immunoprecipitation (RIP) assay, RNA stability experiment and western blots were conducted to explore the molecular regulation of GBE1 in PC. Results: GBE1 was significantly upregulated in PC and associated with poor prognosis of PC patients. Functionally, GBE1 overexpression facilitated PC cell proliferation and stemness-like properties, while knockdown of GBE1 attenuated the malignancy of PC cells. Importantly, we found the m6A modification of GBE1 RNA, and WTAP and IGF2BP3 was revealed as the m6A regulators to increase GBE1 mRNA stability and expression. Furthermore, c-Myc was discovered as a downstream gene of GBE1 and functional rescue experiments showed that overexpression of c-Myc could rescue GBE1 knockdown-induced PC cell growth inhibition. Conclusions: Our study uncovered the oncogenic role of GBE1/c-Myc axis in PC progression and revealed WTAP/IGF2BP3-mediated m6A modification of GBE1, which highlight the potential application of GBE1 in the targeted therapy of PC. Keywords: Pancreatic cancer, GBE1, m6A modification, IGF2BP3, WTAP, Proliferation © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated o

FAQs

What is the study’s main focus in pancreatic cancer cells?

The study focuses on how WTAP/IGF2BP3-mediated m6A modification controls GBE1 expression and thereby accelerates proliferation and enhances stemness-like properties in pancreatic cancer cells.

How did the researchers assess GBE1’s effect on cell behavior?

They measured cell proliferation and stemness using CCK-8, colony formation, sphere formation, and flow cytometry in vitro, and validated functions in vivo using subcutaneous and orthotopic mouse models.

Which molecular regulators connect WTAP/IGF2BP3 to GBE1 and c-Myc?

WTAP and IGF2BP3 act as m6A regulators that increase GBE1 mRNA stability and expression; c-Myc is identified as a downstream gene, and overexpression of c-Myc rescues the growth inhibition caused by GBE1 knockdown.

Sep 22, 2026

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