TNIK overexpression

In summary, we proposed a novel regulatory mechanism in which TNIK-mediated cytoskeleton remodeling and cell migration to regulate tumor progression in PTC. TNIK is a therapeutic target in PTC and NCB-0846 would act as a novel targeted drug for PTC therapy.

The combination of NCB-0846 with cisplatin or etoposide was at best additive. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in LSCC patients with high TNIK expression.

Furthermore, our results showed that the Wnt/β-catenin pathway was inhibited by its specific inhibitor XAV-939, but miR-5590-3p inhibitor and adenoviral TNIK overexpression vector (Ad-TNIK) reactivated the activation of Wnt/β-catenin signaling and increased cell malignancy. Lastly, tumorigenicity assay demonstrated that inhibition of miR-5590-3p increased tumor volume and weight in vivo. In conclusion, miR-5590-3p may function as a cancer suppressor gene in OC progression through the Wnt/β-catenin signaling by transcriptionally suppressing TNIK expression, which provides a potential therapeutic approach for ovarian cancer treatment.