Abstract
Background:
Pancreatic cancer remains one of the most fatal tumors, with a 5-year survival rate of less than 10%, owing mostly to late-stage detection and inadequate treatment efficiency. The pressing need for novel diagnostic and therapeutic approaches has sparked interest in genetic biomarkers and ultrasound-based precision therapies. Circular RNAs (circRNAs) have recently been identified as intriguing regulatory molecules with diagnostic, prognostic, and therapeutic applications.
Methods:
A comprehensive study of transcriptome and clinical datasets revealed that hsa_circ_0004870 is significantly elevated in pancreatic cancer tissues and is linked with poor patient outcomes. Functional tests, including colony formation, cell counting kit-8, flow cytometry, wound healing, and Transwell invasion studies, were used to evaluate its biological roles. Bioinformatic predictions, along with dual-luciferase reporter assays, revealed the hsa_circ_0004870/miR-3124-3p/TRIM24 regulatory axis. In vivo xenograft research and immunohistochemistry analyses supported these findings. In addition, the authors developed an ultrasound-mediated biophysical modulation model to investigate the potential therapeutic control of this axis.
Results:
hsa_circ_0004870 was highly overexpressed in pancreatic cancer cells, which increased proliferation, migration, and invasion. It acts as a competitive endogenous RNA, sequestering miR-3124-3p, resulting in increased TRIM24 and tumorigenic behavior. In vivo, silencing hsa_circ_0004870 reduced tumor development significantly. Combining these findings with developments in ultrasound-targeted gene and molecular delivery technology suggests that ultrasound-mediated manipulation of the hsa_circ_0004870 axis might provide a precise and noninvasive therapeutic method to overcome resistance and enhance localized cancer management.
Conclusions:
hsa_circ_0004870 was overexpressed in pancreatic cancer cells, resulting in enhanced proliferation, migration, and invasion. It works as a competitive endogenous RNA, sequestering miR-3124-3p, leading to enhanced TRIM24 and tumorigenic behavior. In vivo, suppressing hsa_circ_0004870 dramatically decreased tumor growth. Combining these findings with advances in ultrasound-targeted gene and molecular delivery technology, it appears that ultrasound-mediated manipulation of the hsa_circ_0004870 axis could provide a precise and noninvasive therapeutic method for overcoming resistance and improving localized cancer management.
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