Mohammad Hossein Konyavi - Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
Sadra Salehi-Mazandarani - Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Parvaneh Nikpour - Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Background: Hepatocellular carcinoma (HCC) is the most frequent kind of liver cancer and the fourthleading cause of cancer-related death globally. Circular RNAs (circRNAs), as a type of non-coding RNAs,have been noticed in recent years due to their important features. CircRNAs can function as microRNAsponges and transcription modulators, and can interact with RNA-binding proteins. According to studies,circRNAs can play a significant role in cellular metabolism, which can help us to identify new cancerbiomarkers and therapeutic targets. In this study, we determined differentially expressed circRNAs in HCCand recognized their potentially related molecular pathways.Materials and Methods: Two HCC datasets, including GSE۹۴۵۰۸ (۵ cancerous and ۵ paracanceroussamples) and GSE۹۷۳۳۲ (۷ cancerous and ۷ paracancerous samples) were selected from the Gene ExpressionOmnibus (GEO) database to identify differentially expressed circRNAs (DECs). These two datasets werecombined, and the batch effect was eliminated using the sva R package. The limma R package was then usedto identify DECs with threshold of |log۲FC| > ۲ and adjusted p-value < ۰.۰۵. Subsequently, theCircInteractome database was utilized to detect microRNAs interacting with the DECs based on the context+score percentile ≥ ۹۰. Furthermore, DIANA-miRPath v.۳ was used to reveal molecular pathways relating tothese microRNAs (p-value < ۰.۰۱).Results: Nine DECs (including five upregulated and four downregulated) were identified between cancerousand paracancerous HCC samples. ۵۷ unique microRNAs interacting with the DECs were revealed. Finally,the mirPath database demonstrated ۴۴ significant signaling pathways such as proteoglycans in cancer, Fattyacid biosynthesis, hippo signaling pathway, and adherens junction, which are cancer-associated.Conclusion: This study provides an overview of differentially expressed circRNAs in HCC that are linkedto cancer-related pathways as microRNA sponges. Further research can uncover the precise processes bywhich circRNAs function in HCC.

Carcinoma, Hepatocellular; RNA, Circular; MicroRNAs; Bioinformatic