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Updated: Jul 12, 2025
In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in Preclinical In Vivo Models
Ulrich H Weidle1, Adam Nopora2
1Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany weidle49@t-online.de.
Abstract:
Hepatocellular carcinoma (HCC) ranges as number two with respect to the incidence of tumors and is associated with a dismal prognosis. The therapeutic efficacy of approved multi-tyrosine kinase inhibitors and checkpoint inhibitors is modest. Therefore, the identification of new therapeutic targets and entities is of paramount importance. We searched the literature for up-regulated circular RNAs (circRNAs) which mediate efficacy in preclinical in vivo models of HCC. Our search resulted in 14 circRNAs which up-regulate plasma membrane transmembrane receptors, while 5 circRNAs induced secreted proteins. Two circRNAs facilitated replication of Hepatitis B or C viruses. Three circRNAs up-regulated high mobility group proteins. Six circRNAs regulated components of the ubiquitin system. Seven circRNAs induced GTPases of the family of ras-associated binding proteins (RABs). Three circRNAs induced redox-related proteins, eight of them up-regulated metabolic enzymes and nine circRNAs induced signaling-related proteins. The identified circRNAs up-regulate the corresponding targets by sponging microRNAs. Identified circRNAs and their targets have to be validated by standard criteria of preclinical drug development. Identified targets can potentially be inhibited by small molecules or antibody-based moieties and circRNAs can be inhibited by small-interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) for therapeutic purposes.
Insights
Researchers identified novel circular RNAs (circRNAs) that show promise for treating hepatocellular carcinoma (HCC). These circRNAs target various proteins, offering new therapeutic strategies for this challenging cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death with limited effective treatments.
- Current therapies, including tyrosine kinase and checkpoint inhibitors, offer modest benefits.
- There is a critical need for novel therapeutic targets and agents for HCC management.
Purpose of the Study:
- To identify up-regulated circular RNAs (circRNAs) in hepatocellular carcinoma (HCC) that are effective in preclinical models.
- To explore the therapeutic potential of these identified circRNAs and their downstream targets.
Main Methods:
- Literature search for preclinical in vivo studies of HCC.
- Identification and categorization of up-regulated circRNAs based on their targeted molecules.
- Analysis of circRNA-microRNA sponging mechanisms.
Main Results:
- 14 circRNAs up-regulated transmembrane receptors; 5 induced secreted proteins.
- 2 circRNAs influenced Hepatitis B/C virus replication; 3 up-regulated high mobility group proteins.
- 6 circRNAs regulated the ubiquitin system; 7 induced RAB GTPases; 3 induced redox proteins; 8 up-regulated metabolic enzymes; 9 induced signaling proteins.
- Identified circRNAs function by sponging microRNAs to up-regulate their targets.
Conclusions:
- Numerous circRNAs and their targets represent promising avenues for HCC therapy.
- Validated circRNAs and targets can be inhibited by small molecules, antibodies, or RNA-based therapeutics (siRNAs, shRNAs).
- Further preclinical validation is essential for drug development.
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