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CircRNAs in Pancreatic Cancer: New Tools for Target Identification and Therapeutic Intervention
Ulrich H Weidle1, Adam Nopora2
1Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany weidle49@t-online.de.
Abstract:
We have reviewed the literature for circular RNAs (circRNAs) with efficacy in preclinical pancreatic-cancer related in vivo models. The identified circRNAs target chemoresistance mechanisms (n=5), secreted proteins and transmembrane receptors (n=15), transcription factors (n=9), components of the signaling- (n=11), ubiquitination- (n=2), autophagy-system (n=2), and others (n=9). In addition to identifying targets for therapeutic intervention, circRNAs are potential new entities for treatment of pancreatic cancer. Up-regulated circRNAs can be inhibited by antisense oligonucleotides (ASO), small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs) or clustered regularly interspaced short-palindromic repeats-CRISPR associated protein (CRISPR-CAS)-based intervention. The function of down-regulated circRNAs can be reconstituted by replacement therapy using plasmids or virus-based vector systems. Target validation experiments and the development of improved delivery systems for corresponding agents were examined.
Insights
Circular RNAs (circRNAs) show promise for pancreatic cancer treatment by targeting key mechanisms. Therapeutic strategies include inhibiting up-regulated circRNAs or replacing down-regulated ones in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic cancer remains a significant health challenge with limited effective treatments.
- Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, including pancreatic cancer.
- Understanding the role of circRNAs in pancreatic cancer pathogenesis is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To review and identify circular RNAs (circRNAs) with demonstrated efficacy in preclinical pancreatic cancer models.
- To explore the therapeutic potential of circRNAs by analyzing their targeted mechanisms.
- To evaluate existing and potential therapeutic interventions targeting circRNAs in pancreatic cancer.
Main Methods:
- Literature review of preclinical in vivo studies on circRNAs in pancreatic cancer.
- Categorization of identified circRNAs based on their targeted biological mechanisms.
- Analysis of therapeutic strategies for modulating circRNA expression and function.
Main Results:
- A comprehensive list of circRNAs targeting chemoresistance, secreted proteins, transcription factors, signaling pathways, ubiquitination, and autophagy was identified.
- Identified circRNAs represent potential therapeutic targets for pancreatic cancer intervention.
- Various therapeutic modalities, including antisense oligonucleotides (ASO), siRNAs, shRNAs, CRISPR-CAS, and replacement therapies, were examined for their efficacy.
Conclusions:
- Circular RNAs (circRNAs) are promising therapeutic targets and agents for pancreatic cancer.
- Modulating circRNA expression through inhibition or replacement offers potential treatment avenues.
- Further research into target validation and delivery systems is essential for clinical translation.
