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.

Keywords: RRM2; DEAD-box RNA helicase 10; Pancreatic cancer proliferation; Migration; Invasion

Core Tip: This study elucidates the role of DEAD-box RNA helicase 10 (DDX10) in pancreatic cancer (PC) progression. Through bioinformatics analysis, tissue microarray evaluation, and in vitro assays, we discovered that DDX10 is overexpressed in PC tissues compared to non-tumor tissues. Knockdown of DDX10 significantly inhibited cell proliferation, invasion, and migration while promoting apoptosis. Mechanistic investigations revealed that DDX10 regulates key oncogenes, including RRM2, which counteracts the growth-inhibitory effects of DDX10 knockdown. Importantly, DDX10 expression was found to negatively correlate with patient survival rates. These findings highlight DDX10 as a potential therapeutic target for PC.