An emerging research: the role of hepatocellular carcinoma-derived exosomal circRNAs in the immune microenvironment.

Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, is one of the leading causes of cancer-related death and is associated with a poor prognosis. The tumor microenvironment (TME) of HCC comprises immune, immunosuppressive, and interstitial cells with hypoxic, angiogenic, metabolic reprogramming, inflammatory, and immunosuppressive features. Exosomes are nanoscale extracellular vesicles that secrete biologically active signaling molecules such as deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), microribonucleic acid (miRNA), proteins, and lipids. These signaling molecules act as messengers in the tumor microenvironment, especially the tumor immunosuppressive microenvironment. Exosomal circRNAs reshape the tumor microenvironment by prompting hypoxic stress response, stimulating angiogenesis, contributing to metabolic reprogramming, facilitating inflammatory changes in the HCC cells and inducing tumor immunosuppression. The exosomes secreted by HCC cells carry circRNA into immune cells, which intervene in the activation of immune cells and promote the overexpression of immune checkpoints to regulate immune response, leading tumor cells to acquire immunosuppressive properties. Furthermore, immunosuppression is the final result of a combination of TME-related factors, including hypoxia, angiogenesis, metabolic reprogramming, and inflammation changes. In conclusion, exosomal circRNA accelerates the tumor progression by adjusting the phenotype of the tumor microenvironment and ultimately forming an immunosuppressive microenvironment. HCC-derived exosomal circRNA can affect HCC cell proliferation, invasion, metastasis, and induction of chemoresistance. Therefore, this review aimed to summarize the composition and function of these exosomes, the role that HCC-derived exosomal circRNAs play in microenvironment formation, and the interactions between exosomes and immune cells. This review outlines the role of exosomal circRNAs in the malignant phenotype of HCC and provides a preliminary exploration of the clinical utility of exosomal circRNAs.

Identification of Key Carcinogenic Genes in Colon Adenocarcinoma.

Background: We aimed to probe carcinogenic genes associated with colon adenocarcinoma (COAD) development. Methods: The gene expression profile of COAD were downloaded from TCGA. Differentially expressed genes (DEGs) were identified; GO and KEGG pathway enrichment were analyzed. Applying the up-mRNA-and-down-miRNA pairs and the down-mRNA-and-up-miRNA pairs, the miRNA target network was generated. The important genes were further analyzed towards the influence on overall survival and immune infiltration. In addition, essential miRNAs were selected for expression validation using real-time qPCR. Results: Together, from 2020-2021, in Central Laboratory of the Second Affiliated Hospital of Fujian Medical University, we found 3060 up-regulated transcripts and 2254 down-regulated transcripts in mRNA expression, with 235 up-regulated and 263 down-regulated miRNAs. We discovered 98 enriched GO terms using the up-regulated DEGs and 315 enriched GO terms using downregulated DEGs. There were 14 enriched KEGG pathways based on the down-regulated DEGs and only one pathway based on the up-regulated DEGs. There were 61 up-mRNA-and-down-miRNA pairs, including 7 miRNAs and 41 carcinogenic targets, among which HOXC13, FOXL2NB, ALOXE3, and ZIC2 were found related to a poorer OS. ZIC2 located at the subnet with the most targets (the miR-129-5p subnet). ZIC2 expression was correlated with immune-cell infiltration. Conclusion: These risk genes, interaction networks, and enrichments may provide a better understanding of the complex molecular mechanisms in COAD development and potential therapeutic targets for clinical treatment of COAD.