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HMGA2过表达通过m6A修饰激活IGF2BP2以稳定APLP2并促进胰腺癌进展。

HMGA2 overexpression activates IGF2BP2 to stabilize APLP2 via m6A modification and promote pancreatic cancer progression.

作者信息

Liu Ke, Wei Congbing, Yu Haixin, Zhang Qun, Du Zhouyuan

机构信息

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Hospital of China University of Geosciences (Wuhan), Wuhan, 430074, China.

出版信息

Heliyon. 2024 Feb 28;10(5):e27268. doi: 10.1016/j.heliyon.2024.e27268. eCollection 2024 Mar 15.

DOI:10.1016/j.heliyon.2024.e27268
PMID:38449630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10915557/
Abstract

Pancreatic cancer is a highly aggressive malignancy of the digestive system, with occult onset, rapid progression, and poor prognosis. The genetic heterogeneity of pancreatic cancer contributes to its highly malignant biological behavior. HMGA2 is overexpressed in tumors and is known to regulate tumor progression in various cancers through the HMGA2-IGF2BP2 axis, but its role and mechanism in pancreatic cancer remain unclear. In this study, we demonstrated that HMGA2 promotes pancreatic cancer progression. We further revealed that HMGA2 upregulates IGF2BP2, which stabilizes APLP2 mRNA via m6A modification, thereby promoting pancreatic cancer progression. These results indicate that HMGA2/IGF2BP2/APLP2 signaling axis regulates the progression of pancreatic cancer.

摘要

胰腺癌是消化系统一种侵袭性很强的恶性肿瘤，起病隐匿，进展迅速，预后较差。胰腺癌的基因异质性导致其具有高度恶性的生物学行为。HMGA2在肿瘤中过表达，已知其通过HMGA2-IGF2BP2轴调节多种癌症的肿瘤进展，但其在胰腺癌中的作用和机制仍不清楚。在本研究中，我们证明HMGA2促进胰腺癌进展。我们进一步揭示，HMGA2上调IGF2BP2，后者通过m6A修饰使APLP2 mRNA稳定，从而促进胰腺癌进展。这些结果表明，HMGA2/IGF2BP2/APLP2信号轴调节胰腺癌的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/5d564e47e611/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/3cb70e56914f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/8955a37cbd7e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/3dd3633007eb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/a085b7c12045/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/5d564e47e611/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/3cb70e56914f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/8955a37cbd7e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/3dd3633007eb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/a085b7c12045/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388b/10915557/5d564e47e611/gr5.jpg

相似文献

[1]
HMGA2 overexpression activates IGF2BP2 to stabilize APLP2 via m6A modification and promote pancreatic cancer progression.

Heliyon. 2024-2-28

[2]
IGF2BP2 promotes pancreatic carcinoma progression by enhancing the stability of B3GNT6 mRNA via m6A methylation.

Cancer Med. 2023-2

[3]
RNA N6-methyladenosine reader IGF2BP2 promotes lymphatic metastasis and epithelial-mesenchymal transition of head and neck squamous carcinoma cells via stabilizing slug mRNA in an m6A-dependent manner.

J Exp Clin Cancer Res. 2022-1-3

[4]
IGF2BP2 serves as a core m6A regulator in head and neck squamous cell carcinoma.

Biosci Rep. 2022-11-30

[5]
Pancancer analysis uncovers an immunological role and prognostic value of the m6A reader IGF2BP2 in pancreatic cancer.

Mol Cell Probes. 2024-2

[6]
CCN6 regulates IGF2BP2 and HMGA2 signaling in metaplastic carcinomas of the breast.

Breast Cancer Res Treat. 2018-9-15

[7]
METTL3/IGF2BP2 axis affects the progression of colorectal cancer by regulating m6A modification of STAG3.

Sci Rep. 2023-10-12

[8]
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Med Oncol. 2022-1-29

[9]
IGF2BP2 Promotes Liver Cancer Growth Through an m6A-FEN1-Dependent Mechanism.

Front Oncol. 2020-11-2

[10]
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引用本文的文献

[1]
Recent Findings in N6-Methyladenosine Modification and Significance in Pancreatic Cancer.

Cancer Med. 2025-6

[2]
Multifaceted roles of insulin‑like growth factor 2 mRNA binding protein 2 in human cancer (Review).

Mol Med Rep. 2025-3

本文引用的文献

[1]
HMGA2 regulation by miRNAs in cancer: Affecting cancer hallmarks and therapy response.

Pharmacol Res. 2023-4

[2]
Cancer statistics, 2023.

CA Cancer J Clin. 2023-1

[3]
CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of mA-modified CREB1 mRNA.

Mol Cancer. 2022-6-30

[4]
HMGA2 facilitates colorectal cancer progression via STAT3-mediated tumor-associated macrophage recruitment.

Theranostics. 2022

[5]
Systemic Therapy for Metastatic Pancreatic Cancer.

Curr Treat Options Oncol. 2021-10-19

[6]
Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer.

Int J Mol Sci. 2021-5-8

[7]
Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer.

Cancers (Basel). 2021-3-26

[8]
The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers.

Cancer Cell Int. 2021-2-10

[9]
The Diverse Functions of IMP2/IGF2BP2 in Metabolism.

Trends Endocrinol Metab. 2020-9

[10]
Overexpression of HMGA2 in breast cancer promotes cell proliferation, migration, invasion and stemness.

Expert Opin Ther Targets. 2020-3

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