DEAD/H-box RNA helicase 10 promotes pancreatic cancer cell proliferation via ribonucleotide reductase M2.

Abstract

Background: Pancreatic cancer (PC) remains one of the most aggressive malignancies, is characterized by rapid progression and high metastatic potential, and is the fourth leading cause of cancer-related mortality worldwide. The incidence and mortality rates of PC continue to rise annually. Despite advances in imaging technologies and treatment strategies over the past two decades, the 5-year survival rate for patients with PC remains low, at approximately 13%. Patients with advanced PC still experience dismal outcomes, primarily due to the tumor's aggressiveness and high metastatic capacity. Thus, there is an urgent need to identify reliable molecular biomarkers and therapeutic targets to improve the prognosis of patients with PC.

Aim: To investigate the biological functions and mechanisms of DEAD/H-box RNA helicase 10 (DDX10) in PC progression.

Methods: We comprehensively investigated the expression pattern and functional significance of DDX10 in PC using a multi-omics integrative approach. We performed bioinformatics analyses of datasets from The Cancer Genome Atlas and Gene Expression Omnibus, tissue microarray-based immunohistochemistry, and a series of in vitro functional assays to assess cellular proliferation, migration, invasion, and apoptosis. Additionally, transcriptomic and proteomic analyses were integrated to delineate the molecular regulatory networks that mediate the aggressive phenotype of PC.

Results: DDX10 was found to be significantly overexpressed at both the mRNA and protein levels in PC tissues compared with adjacent non-tumor tissues. Silencing DDX10 in vitro led to marked inhibition of PC cell proliferation, migration, and invasion, accompanied by enhanced apoptosis. Integrated RNA sequencing, proteomic profiling, and western blot validation revealed that DDX10 modulates key oncogenes including RRM2, LIG1, CDK6, and ITGA2. Notably, ectopic RRM2 overexpression partially rescued the growth-suppressive effects induced by DDX10 knockdown in PANC-1 cells, and high DDX10 expression is associated with poor overall survival in patients with PC.

Conclusion: Collectively, our findings indicate that DDX10 promotes PC cell proliferation primarily by upregulating RRM2, thus highlighting its potential as a promising therapeutic target in PC.