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Updated: Jul 9, 2025

Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
Circular RNA in Non-small Cell Lung Carcinoma: Identification of Targets and New Treatment Modalities
Ulrich H Weidle1, Fabian Birzele2
1Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany; weidle49@t-online.de.
Abstract:
Despite availability of several treatment options for non-small cell lung cancer (NSCLC), such as surgery, chemotherapy, radiation, targeted therapy and immunotherapy, the survival rate of patients for five years is in the range of 22%. Therefore, identification of new targets and treatment modalities for this disease is an important issue. In this context, we screened the PubMed database for up-regulated circular RNAs (circRNAs) which promote growth of NSCLC in preclinical models in vitro as well as in vivo xenograft models in immuno-compromised mice. This approach led to potential targets for further validation and inhibition with small molecules or antibody-derived entities. In case of preclinical validation, the corresponding circRNAs can be inhibited with small interfering RNAs (siRNA) or short hairpin RNAs (shRNA). The identified circRNAs act by sponging microRNAs (miRs) preventing cleavage of the mRNA of the corresponding targets. We identified nine circRNAs up-regulating transmembrane receptors, five circRNAs increasing expression of secreted proteins, nine circRNAs promoting expression of components of signaling pathways, six circRNAs involved in regulation of splicing and RNA processing, six circRNAs up-regulating actin-related and RNA processing components, seven circRNAs increasing the steady-state levels of transcription factors, two circRNAs increasing high-mobility group proteins, four circRNAs increasing components of the epigenetic modification system and three circRNAs up-regulating protein components of additional systems.
Insights
New research identifies circular RNAs (circRNAs) that promote non-small cell lung cancer (NSCLC) growth. Targeting these circRNAs offers potential new therapeutic strategies for this challenging disease.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Non-small cell lung cancer (NSCLC) has a poor five-year survival rate (22%) despite existing treatments.
- Novel therapeutic targets and treatment modalities are crucial for improving NSCLC patient outcomes.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression.
Purpose of the Study:
- To identify up-regulated circRNAs that promote NSCLC growth in preclinical models.
- To explore circRNAs as potential therapeutic targets for NSCLC.
- To investigate the mechanisms by which circRNAs influence NSCLC progression.
Main Methods:
- PubMed database screening for up-regulated circRNAs in NSCLC.
- Evaluation of identified circRNAs in in vitro and in vivo (xenograft) preclinical models.
- Analysis of circRNA-microRNA (miR) interactions and their downstream effects on gene expression.
Main Results:
- Identified multiple circRNAs promoting NSCLC growth by up-regulating transmembrane receptors, secreted proteins, signaling pathways, splicing factors, transcription factors, and epigenetic modifiers.
- Demonstrated circRNAs function by sponging miRs, thereby preventing mRNA cleavage.
- Cataloged specific circRNAs involved in various oncogenic processes, including regulation of actin and high-mobility group proteins.
Conclusions:
- circRNAs represent promising novel targets for NSCLC therapy.
- Inhibition of identified circRNAs using small interfering RNAs (siRNA) or short hairpin RNAs (shRNA) is a viable preclinical strategy.
- Further validation of these circRNAs could lead to the development of small molecule or antibody-based therapies.
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