JOSD2 plays a crucial role in enhancing the proliferation, migration, and drug resistance of ESCC, suggesting that JOSD2 is a potential therapeutic target in ESCC.

Notably, we identified the first small-molecule inhibitor of JOSD2, and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo. Our findings highlight the vital role of JOSD2 in hindering LKB1 activity, underscoring the therapeutic potential of targeting JOSD2 in NSCLC, especially in those with inactivated LKB1, and presenting its inhibitors as a promising strategy for NSCLC treatment.

We identified CDC42 as a pivotal gene in the pathophysiology of HPV-related cancers. The upregulation of CDC42 could be a signal for afatinib treatment and the mechanism in which may be an increased affinity of EGFR to afatinib, inferred from a high stability in the quaternary complex of CDC42-GTPase-effector interface-EGFR-afatinib.

An MCL-1 inhibitor overcame radioresistance in vitro and in vivo. Altogether, the present findings suggest that TRAF4 confers radioresistance in OSCC by stabilizing MCL-1 through Akt signaling, and that targeting TRAF4 may be a promising therapeutic strategy to overcome radioresistance in OSCC.

Taken together, our results indicated that the aberrant expression of MJDs family in HCC played a critical role in clinical feature, prognosis, tumor microenvironment, immune-related molecules, mutation, gene copy number, and promoter methylation level. And MJDs family may be effective immunotherapeutic targets for patients with HCC and have the potential to be prognostic biomarkers.

Finally, JOSD2 decreases AML progression in vivo. Taken together, we propose that JOSD2 blocks PKM2 nuclear localization and reduces AML progression.

Furthermore, a series of rescue experiments confirmed the significance of CTNNB1 in the modulation of HCC progression by JOSD2. Our study uncovered JOSD2 as a novel prognostic marker for patients with HCC and identified CTNNB1 as a pivotal partner and downstream target protein of JOSD2, which may aid in the development of JOSD2 as a promising molecular target for HCC treatment.

Moreover, JOSD1 and Snail co-overexpression had the worst prognosis in LUAD patients. Overall, these results demonstrated that JOSD1 was significantly overexpressed in LUAD and stabilized Snail via deubiquitination to promote LUAD metastasis.

Differentially expressed genes for this naïve-B cell subset includes KLF9, BCL2L11, JOSD1, and IRS2, etc. Overall, as part of MMRF immune profiling research, this study will help to interrogate how genetic alterations and disease progression interplay MM tumor and TME and provide a sufficiently broad and valuable dataset for systematically characterizing MM at single-cell resolution. Hopefully, this study could identify novel targets for MM immunotherapies, and ultimately identify patients with high risk of fast progression for early intervention in the clinic.

JAK2 kinase inhibitors, such as ruxolitinib, provide clinical benefit, but inhibition of wild-type (wt) JAK2 limits their clinical utility due to toxicity to normal cells, and small molecule inhibition of mutated JAK2 kinase activity can lead to drug resistance...Moreover, targeting of JOSD1 leads to the death of JAK2-V617F-positive primary acute myeloid leukemia (AML) cells. These studies provide a novel therapeutic approach to achieving selective targeting of mutated JAK2 signaling in MPN.

These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

Through this comprehensive approach, the present study illustrated the scheme of how NO affects molecular events in lung cancer cells.