Long Non-Coding RNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Regulation, Functions, and Underlying Mechanisms

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death in the world. Hepatitis B virus (HBV) and its X gene-encoded protein (HBx) play important roles in the progression of HCC. Although long non-coding RNAs (lncRNAs) cannot encode proteins, growing evidence indicates that they play essential roles in HCC progression, and contribute to cell proliferation, invasion and metastasis, autophagy, and apoptosis by targeting a large number of pivotal protein-coding genes, miRNAs, and signaling pathways. In this review, we briefly outline recent findings of differentially expressed lncRNAs in HBV-related HCC, with particular focus on several key lncRNAs, and discuss their regulation by HBV/HBx, their functions, and their underlying molecular mechanisms in the progression of HCC.

Keywords: HBV; HBx; HCC; apoptosis; autophagy; epithelial-mesenchymal transition; invasion and metastasis; lncRNAs; proliferation.

Figure 1

Dysregulated long non-coding RNAs (lncRNAs) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and their functions in HCC progression, including the modulation of HCC cell proliferation, invasion and metastasis, autophagy, and apoptosis [3,11,12,13,14,15,16,17,18,19,20,21,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43].

Figure 2

Several key lncRNAs aberrantly expressed in HBV-related HCC, their targets, and their underlying molecular mechanisms in HCC progression. (A) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1); (B) HULC (highly upregulated in liver cancer); (C) UCA1 (urothelial carcinoma associated-1); (D) HOTAIR (HOX transcript antisense intergenic RNA); (E) H19 (imprinted maternally expressed untranslated mRNA); (F) MVIH (microvascular invasion in HCC).