Novel CircRNAs in Hub ceRNA Axis Regulate Gastric Cancer Prognosis and Microenvironment

Abstract

Gastric cancer (GC) is one of the most prevalent malignancies with an unfavorable survival rate. Immunotherapy may contribute to a better prognosis. However, several phase III trials failed. Circular RNA (circRNA) is a novel type of non-coding RNA, plays a vital role in the progression of tumors. The expression and function of circRNA in the GC immune microenvironment remain obscure. In this study, we utilized a bioinformatic analysis to construct a circRNA/microRNA (miRNA)/messenger RNA (mRNA) network involved in the progression and prognosis of GC. CircRNA DYRK1A_017, circRNA FLNA_118, miR-6512-3p, miR-6270-5p, and VCAN were identified as the key molecules in the hub regulatory axis. Dysregulation of this axis contributed to the cancer-associated signaling pathways (epithelial-mesenchymal transition [EMT], Nuclear factor kappa β-Tumor necrosis factor-α (NFκβ-TNFα) signaling, and angiogenesis) and aberrant immune microenvironment (infiltration by tumor associated macrophage, regulatory T cell, and mast cell). More importantly, the immunosuppressive tumor microenvironment may reveal the mechanism of novel circRNAs in tumors and serve as the target of immunotherapy.