Role of Noncoding RNAs in the Tumor Immune Microenvironment of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies. It has high mortality and poor clinical outcomes, but the molecular mechanisms in the pathogenesis of HCC are not understood. The tumor immune microenvironment (TIME) is a highly intricate system with distinct populations of innate and adaptive immune cells, as well as other stromal cells. They interact and evolve with tumor cells to influence tumor growth, migration, invasion, immune evasion, and response to therapy. Emerging evidence has shown noncoding RNAs (ncRNAs) are prominent regulators of TIME in HCC. In this review, we elaborate on the functions and molecular mechanisms of ncRNAs in remodeling TIME of HCC and discuss their diagnostic and therapeutic potential for HCC treatment.

Keywords: Biomarker; HCC; TIME; Therapeutic strategy; ncRNAs.

Fig. 1. Key players in the TIME of HCC.

The TIME of HCC is a highly sophisticated system consisting of diverse cellular and noncellular components. The cellular components comprise various immune cells (macrophages, neutrophils, myeloid-derived suppressor cells, natural killer cells, dendritic cells, T cells, B cells), endothelial cells, cancer-associated fibroblasts, and other kinds of stromal cells. The noncellular counterparts include the extracellular matrix and diverse soluble factors secreted by both tumor cells and stromal cells. HCC, hepatocellular carcinoma; TIME, tumor immune microenvironment.

Fig. 2. ncRNA-mediated regulation of TIME. ncRNAs (miRNAs/lncRNAs/circRNAs) regulate the development, activation, recruitment, and cellular function of multiple cell types within TIME of HCC by diverse mechanisms.

CAF, cancer-associated fibroblast; circ, circular RNA; HCC, hepatocellular carcinoma; HSC, hepatic stellate cell; lnc, long noncoding RNA; MDSC, myeloid-derived suppressor cell; NK, natural killer; Treg, regulatory T cell; TIME, tumor immune microenvironment.