LRIG2 (Leucine Rich Repeats And Immunoglobulin Like Domains 2)

Additionally, abnormal stress adaptations of the UFM1 conjugation system contribute to the pathophysiological complications of inflammatory diseases and cancer, underscoring its significance as a key regulatory node in human health and disease. Therefore, this review provides a comprehensive exploration of the structural characteristics of UFM1 conjugation system members and the mechanistic roles of UFMylation by UFM1 conjugation system-mediated diseases related to cellular stress responses, which will not only facilitate the identification of novel diagnostic and prognostic indicators but also enable the identification of specific therapeutic targets for UFM1 conjugation system-related diseases.

Furthermore, exogenous expression of the E3 ligase components UFM1-specific ligase 1 (UFL1) and DDRGK domain-containing protein 1 (DDRGK1) significantly enhances protein UFMylation levels, enabling the large-scale enrichment of UFMylated substrates. Collectively, we have established a more efficient, specific, and reliable method for UFMylation substrates research, facilitating in-depth investigation into its biological functions and regulatory mechanisms.

LRIG3 mRNA expression, in contrast, was significantly higher in grade II gliomas compared to surrounding control tissue, whereas chemotherapy did not significantly affect expression levels in glioblastoma. Our results reinforce suggestions that LRIG1-3 could function as diagnostic markers and therapeutic targets in the treatment of gliomas.

Among these, overexpression of PCMTD2 and AL391840.2 represented risk factors, while RBM43 and LRIG2 were identified as protective factors in ESCA. Berberine may inhibit ESCA progression by modulating CCDC18-AS1 expression, thereby improving patient prognosis.

This integrative analysis identify potential biomarkers associated with 5-FU and Oxaliplatin response, nominating ALDH9A1, FERMT3, NT5E, HIF1A, and specific microRNAs as resistance biomarkers, while GRIN1, MTHFD2, and miR-7 emerge as sensitizers. Importantly, repurposing opportunities were identified, with statins and kinase inhibitors showing context-dependent associations that may help overcome resistance. These findings may provide a framework for potential biomarkers guided therapy optimization and may inform rational combination strategies in colorectal cancer.

Our findings established the expressed profiles of UFMylaiton in multiple tissues of mice mimicking MASLD, indicating an important regulation for UFMylation in these tissues' homeostasis maintenance.

UFMylation is an important process in CSCs, and mithramycin, or its lesser toxic analogs, should be further explored as CSCs targeted therapy in HNSCC.

Consequently, loss of UFL1, disruption of PTIP UFMylation or overexpression of the UFM1 protease UFSP2 protects nascent DNA strands from extensive degradation and confers resistance to PARP inhibitors in BRCA1/2-deficient cells. These findings provide mechanistic insights into the processes underlying fork instability in BRCA1/2-deficient cells and offer potential therapeutic avenues for the treatment of BRCA1/2-deficient tumors.

Moreover, we identified a covalent inhibitor of UFSP2 that promoted the UFMylation activity and contributed to the combination therapy with PD-1 blockade. Our findings identified a previously unrecognized regulator of PD-L1 and highlighted UFMylation as a potential therapeutic target.

LRIG2 acts as an oncogene in osteosarcoma, and it might become a novel target in the treatment of human OS.

GBM cells with high level LRIG2 escape the phagocytosis by TAM via the CD47-SIRPα axis, highlighting a necessity for an early stage of clinical trial targeting LRIG2 and CD47-SIRPα as a novel treatment for patients with GBM.

Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.