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Updated: Jun 25, 2025
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Spliceosomic dysregulation in pancreatic cancer uncovers splicing factors PRPF8 and RBMX as novel candidate
Emilia Alors-Pérez1,2,3, Ricardo Blázquez-Encinas1,2,3, María Trinidad Moreno-Montilla1,2,3
1Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Spain.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, characterized by late diagnosis and poor treatment response. Surgery is the only curative approach, only available to early-diagnosed patients. Current therapies have limited effects, cause severe toxicities, and minimally improve overall survival. Understanding of splicing machinery alterations in PDAC remains incomplete. Here, we comprehensively examined 59 splicing machinery components, uncovering dysregulation in pre-mRNA processing factor 8 (PRPF8) and RNA-binding motif protein X-linked (RBMX). Their downregulated expression was linked to poor prognosis and malignancy features, including tumor stage, invasion and metastasis, and associated with poorer survival and the mutation of key PDAC genes. Experimental modulation of these splicing factors in pancreatic cancer cell lines reverted their expression to non-tumor levels and resulted in decreased key tumor-related features. These results provide evidence that the splicing machinery is altered in PDAC, wherein PRPF8 and RBMX emerge as candidate actionable therapeutic targets.
Insights
Altered splicing machinery, including pre-mRNA processing factor 8 (PRPF8) and RNA-binding motif protein X-linked (RBMX), is linked to poor prognosis in pancreatic cancer. Downregulated PRPF8 and RBMX suggest potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with late diagnosis and limited treatment options.
- Current therapies for PDAC offer minimal survival benefits and significant toxicities.
- The role of splicing machinery alterations in PDAC pathogenesis is not fully understood.
Purpose of the Study:
- To comprehensively investigate alterations in splicing machinery components in PDAC.
- To identify specific splicing factors associated with PDAC progression and patient prognosis.
- To evaluate the therapeutic potential of targeting identified splicing factors in PDAC.
Main Methods:
- Systematic examination of 59 splicing machinery components in PDAC.
- Correlation analysis of splicing factor expression with clinical parameters and genetic mutations.
- Experimental manipulation of key splicing factors (PRPF8, RBMX) in pancreatic cancer cell lines.
Main Results:
- Dysregulation of pre-mRNA processing factor 8 (PRPF8) and RNA-binding motif protein X-linked (RBMX) was identified in PDAC.
- Downregulated PRPF8 and RBMX expression correlated with advanced tumor stage, invasion, metastasis, and poorer patient survival.
- Experimental restoration of PRPF8 and RBMX levels reduced key tumor-associated features in cell lines.
Conclusions:
- Splicing machinery is significantly altered in PDAC, impacting cancer progression.
- PRPF8 and RBMX are promising candidate biomarkers and actionable therapeutic targets for PDAC.
- Targeting PRPF8 and RBMX may offer a novel therapeutic strategy for pancreatic cancer.
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