Ultrasound-targeted microbubble destruction-mediated silencing of FBXO11 suppresses development of pancreatic cancer.

Abstract

Ultrasound-targeted microbubble destruction (UTMD) has been a promising noninvasive tool for organ- or tissue-specific gene or drug delivery. This study aimed to explore the function of F-box protein 11 (FBXO11), an E3 ubiquitin ligase, in the development of pancreatic cancer (PCa). Differentially expressed genes in PCa were identified using the GSE62452 and GSE28735 datasets, and FBXO11 was significantly highly expressed in PCa. UTMD-mediated FBXO11 silencing significantly suppressed growth activity, epithelial-mesenchymal transition, migration, and invasion while reduced apoptosis of PCa cells in vitro and reduced the growth and metastasis of xenograft tumors in vivo. Importantly, UTMD-mediated sh-FBXO11 showed more pronounced tumor-suppressive effects than direct administration of sh-FBXO11 alone. The potential substrates of FBXO11 as an E3 ubiquitin ligase were predicted using the Ubibrowser. TP53 was predicted and validated as a downstream substrate of FBXO11. FBXO11 induced ubiquitination and degradation of the tumor suppressor protein TP53 to induce PCa progression. In conclusion, this study suggests that silencing of FBXO11, especially that mediated by UTMD, might suppress the malignant biological behaviors of PCa cells and serve as a potential therapeutic strategy for PCa management.