Construction of a circRNA-miRNA-mRNA Network Related to Macrophage Infiltration in Hepatocellular Carcinoma

Abstract

Immune cells in the tumor microenvironment play a crucial role in regulating tumor progression. The circular RNA (circRNA) regulatory network involved in immune cell infiltration in hepatocellular carcinoma (HCC) remains largely unknown. In this study, the "estimate the proportion of immune and cancer cells" (EPIC) application is used to evaluate the fractions of immune cells, cancer-associated fibroblasts, and endothelial cells in HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Patients with a high macrophage fraction have better overall survival, and macrophage fraction is an independent prognostic factor for HCC. Next, the common differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) between paired tumor and non-tumor tissues are screened out from the TCGA and/or GEO databases. Through spearman correlation analysis, the macrophage-related DEmRNAs are identified to construct a circRNA-miRNA-mRNA regulatory network, which includes 6 DEcircRNAs, 7 DEmiRNAs, and 45 DEmRNAs. Functional enrichment analysis reveals that these DEmRNAs are mainly involved in immune-related processes. Furthermore, six hub DEmRNAs are identified to establish a hub circRNA regulatory network. Among the DEmRNAs in the network, PRC1 is identified as the most influential node. PRC1 high expression is correlated with poor prognosis and low macrophage infiltration in HCC. Taken together, we identify a certain circRNA regulatory network related to macrophage infiltration and provide novel insight into the mechanism of study and therapeutic targets for HCC.

Identification of Gene Signature as Diagnostic and Prognostic Blood Biomarker for Early Hepatocellular Carcinoma Using Integrated Cross-Species Transcriptomic and Network Analyses

“…However, alpha-Fetoprotein bears low specificity owing to its presence in other cancer types ( Schütte et al, 2014 ). Recent genomic works focus on using RNA-related approaches such as mRNA ( Wang et al, 2017 ; Guan et al, 2020 ; Zhou et al, 2020 ) and miRNA signatures ( Liu et al, 2017 ; Bai et al, 2018a ), long non-coding RNAs ( Arun et al, 2018 ; Ma et al, 2020 ) targeted mRNAs for critical genes ( Lin et al, 2016 ), and DNA based approaches such as driver mutations or circulating tumor DNAs ( Yang et al, 2019b ; Cai et al, 2019 ). However, some of the highly predictive biomarkers suffer from requiring invasive procedures or not able to detect the early HCC development.…”

Differently Expressed Circular RNAs in Lacrimal Sacs From Patients With Chronic Dacryocystitis

“…CircRNAs have multiple molecular mechanisms, such as nuclear transcriptional regulators of host genes, RNA-binding protein sequestering agents or miRNA sponges ( Li et al, 2018 ). Thus dysregulated circRNAs have been reported to be involved in a lot of disease such as osteoarthritis, cancer and many ocular disorders ( Zhou et al, 2019 ; Cui et al, 2020 ; Zhou et al, 2020 ; Zou et al, 2020 ; Zheng et al, 2021 ). In our study, we performed high-throughput RNA sequencing of the lacrimal sac samples from chronic dacryocystitis patients and control individuals for the first time and constructed circRNA-mRNA and circRNA-miRNA interaction networks trying to throw light on the pathogenesis of chronic dacryocystitis on RNA level.…”

Hsa_circ_0091581 promotes glioma progression by regulating RMI1 via sponging miR-1243-5p

“…To determine the mechanism of action of hsa_circ_0091581 on glioma proliferation, migration, and invasion, we used the results described in the literature that suggested that circRNAs can play a regulatory role by adsorbing miRNAs [30][31][32]. Hsa_circ_0001785 sponges miR-942 to regulate breast cancer progression [33]; hsa_circ_0005556 sponges miR-4270 to facilitate gastric cancer progression [34]; and hsa_circ_0004913 act as a sponge for miR-184 and is thus involved in the progress of hepatocellular carcinoma [35].…”