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

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.