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LIN28B 诱导的 PCAT5 通过 IGF2BP3 去泛素化促进子宫内膜癌的进展和糖酵解。

LIN28B induced PCAT5 promotes endometrial cancer progression and glycolysis via IGF2BP3 deubiquitination.

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang City, Liaoning Province, 110022, China.

出版信息

Cell Death Dis. 2024 Apr 2;15(4):242. doi: 10.1038/s41419-024-06564-2.

DOI:10.1038/s41419-024-06564-2
PMID:38565547
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10987620/
Abstract

Endometrial cancer (EC) cells exhibit abnormal glucose metabolism, characterized by increased aerobic glycolysis and decreased oxidative phosphorylation. Targeting cellular glucose metabolism in these cells could be an effective therapeutic approach for EC. This study aimed to assess the roles of LIN28B, PCAT5, and IGF2BP3 in the glucose metabolism, proliferation, migration, and invasion of EC cells. LIN28B highly expressed in EC, binds and stabilizes PCAT5. PCAT5, overexpressed in EC, and its 1485-2288nt region can bind to the KH1-2 domain of IGF2BP3 to prevent MKRN2 from binding to the K294 ubiquitination site of IGF2BP3, thus stabilizing IGF2BP3. Finally, IGF2BP3 promotes the aerobic glycolysis, proliferation, migration and invasion of EC cells by stabilizing the key enzymes of glucose metabolism HK2 and PKM2. Taken together, our data reveal that the LIN28B/PCAT5/IGF2BP3 axis is critical for glucose reprogramming and malignant biological behavior in EC cells. Therefore, targeting this axis may contribute to the development of a novel therapeutic strategy for EC metabolism.

摘要

子宫内膜癌（EC）细胞表现出异常的葡萄糖代谢，其特征为有氧糖酵解增加和氧化磷酸化减少。针对这些细胞的细胞葡萄糖代谢进行靶向治疗可能是治疗 EC 的一种有效方法。本研究旨在评估 LIN28B、PCAT5 和 IGF2BP3 在 EC 细胞葡萄糖代谢、增殖、迁移和侵袭中的作用。LIN28B 在 EC 中高表达，可与 PCAT5 结合并稳定其表达。PCAT5 在 EC 中过表达，其 1485-2288nt 区域可与 IGF2BP3 的 KH1-2 结构域结合，阻止 MKRN2 与 IGF2BP3 的 K294 泛素化位点结合，从而稳定 IGF2BP3。最后，IGF2BP3 通过稳定葡萄糖代谢的关键酶 HK2 和 PKM2 促进 EC 细胞的有氧糖酵解、增殖、迁移和侵袭。总之，我们的数据表明 LIN28B/PCAT5/IGF2BP3 轴对于 EC 细胞的葡萄糖重编程和恶性生物学行为至关重要。因此，靶向该轴可能有助于开发 EC 代谢的新治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/1f174ed4abc4/41419_2024_6564_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/fe1b57d50f99/41419_2024_6564_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/f132566879f9/41419_2024_6564_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/fc33a85a8a9f/41419_2024_6564_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/2ab7e1143d38/41419_2024_6564_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/bff268440c32/41419_2024_6564_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/75093c392fd6/41419_2024_6564_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/1f174ed4abc4/41419_2024_6564_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/fe1b57d50f99/41419_2024_6564_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/f132566879f9/41419_2024_6564_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/fc33a85a8a9f/41419_2024_6564_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/2ab7e1143d38/41419_2024_6564_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/bff268440c32/41419_2024_6564_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/75093c392fd6/41419_2024_6564_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a791/10987620/1f174ed4abc4/41419_2024_6564_Fig7_HTML.jpg

相似文献

[1]
LIN28B induced PCAT5 promotes endometrial cancer progression and glycolysis via IGF2BP3 deubiquitination.

Cell Death Dis. 2024-4-2

[2]
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[3]
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[4]
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[8]
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[10]
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引用本文的文献

[1]
LIN28B promotes the progression of endometrial cancer through upregulating MYC and correlates with immune microenvironment.

Front Oncol. 2025-7-16

[2]
Mitochondria-related genes as prognostic signature of endometrial cancer and the effect of MACC1 on tumor cells.

PLoS One. 2025-5-12

[3]
Comprehensive analysis of ceRNA Networks in UCEC: Prognostic and therapeutic implications.

PLoS One. 2025-1-30

本文引用的文献

[1]
Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential.

Biomark Res. 2023-6-6

[2]
MRKNs: Gene, Functions, and Role in Disease and Infection.

Front Oncol. 2022-4-8

[3]
EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3.

Mol Cancer. 2022-1-14

[4]
Histone deacetylase 1 facilitates aerobic glycolysis and growth of endometrial cancer.

Oncol Lett. 2021-10

[5]
Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2/miR-181a pathway.

J Exp Clin Cancer Res. 2021-6-26

[6]
LIN28B induces a differentiation program through CDX2 in colon cancer.

JCI Insight. 2021-5-10

[7]
The role of HOTAIR/miR-152-3p/LIN28B in regulating the progression of endometrial squamous carcinoma.

Arch Med Sci. 2019-11-7

[8]
USP11 facilitates colorectal cancer proliferation and metastasis by regulating IGF2BP3 stability.

Am J Transl Res. 2021-2-15

[9]
Construction of a Glycolysis-related long noncoding RNA signature for predicting survival in endometrial cancer.

J Cancer. 2021-1-1

[10]
LNCcation: lncRNA localization and function.

J Cell Biol. 2021-2-1

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