2. Academic Validation
  3. UBE2I promotes immune infiltration and tumor progression in thyroid cancer and modulates hnRNPA2B1 SUMOylation

UBE2I promotes immune infiltration and tumor progression in thyroid cancer and modulates hnRNPA2B1 SUMOylation

  • J Biol Chem. 2025 Dec 20;302(2):111091. doi: 10.1016/j.jbc.2025.111091.
Jinmiao Wang 1,  Minghan Qiu 2,  Li Dong 3,  Jie Hao 1,  Ying Gao 1,  Weijie Tao 1,  Shoujun Wang 1,  Ran Duan 1,  Ming Gao 4
Affiliations

Affiliations

  • 1 Department of Thyroid and Breast Surgery, Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, China.
  • 2 Department of Oncology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, China.
  • 3 Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 4 Department of Thyroid and Breast Surgery, Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, China. Electronic address: [email protected].
PMID: 41429355 DOI: 10.1016/j.jbc.2025.111091
Abstract

Thyroid Cancer (THCA), a frequent endocrine tumor, has been on the rise in recent years. Identifying potential targets and further clarifying the underlying molecular mechanisms are essential for improving the management of THCA. Multiple genetic and epigenetic changes influence the onset and course of THCA. SUMOylation is a critical posttranslational modification (PTM) that has been reported to be involved in THCA. Ubiquitin-conjugating enzyme E2I (UBE2I), which is required for SUMO conjugation, is crucial to the development of different malignancies. Nonetheless, its role in THCA is not completely understood. In this study, we found that UBE2I was upregulated in THCA. Knock-in and knockdown results showed that UBE2I promoted cell growth, migration, and invasion, as well as macrophage M2 polarization in THCA cells. Mechanistically, UBE2I enhanced the localization of hnRNPA2B1 in the cytoplasm by promoting its SUMOylation, and the inhibition of SUMOylation reversed the tumor-promoting effect of UBE2I overexpression in THCA cells. In vivo, downregulation of UBE2I reduced tumor growth and the level of CD206. Taken together, our findings suggest that UBE2I promotes growth, migration, invasion, and M2 polarization of macrophages in THCA cells, potentially through a mechanism involving SUMOylation and the subsequent cytoplasmic localization of hnRNPA2B1.

Keywords

SUMOylation; UBE2I; hnRNPA2B1; migration; polarization; thyroid cancer; tumor-associated macrophage.

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