Non-Coding RNAs: Regulating Disease Progression and Therapy Resistance in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC), the primary liver cancer arising from hepatocytes, is a universal health problem and one of the most common malignant tumors. Surgery followed by chemotherapy as well as tyrosine kinase inhibitors (TKIs), such as sorafenib, are primary treatment procedures for HCC, but recurrence of disease because of therapy resistance results in high mortality. It is necessary to identify novel regulators of HCC for developing effective targeted therapies that can significantly interfere with progression of the disease process. Non-coding RNAs (ncRNAs) are an abundant group of versatile RNA transcripts that do not translate into proteins, rather serve as potentially functional RNAs. The role of ncRNAs in regulating diverse aspects of the carcinogenesis process are gradually being elucidated. Recent advances in RNA sequencing technology have identified a plethora of ncRNAs regulating all aspects of hepatocarcinogenesis process and serving as potential prognostic or diagnostic biomarkers. The present review provides a comprehensive description of the biological roles of ncRNAs in disease process and therapy resistance, and potential clinical application of these ncRNAs in HCC.

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

“… 36 Epigenetic alterations involving the chromatin remodelling machinery and ncRNAs have recently been reviewed elsewhere. [37] , [38] , [39] Herein, we review basic epigenetic mechanisms and the role of their dysregulation on hepatocarcinogenesis, focusing on DNA methylation and histone PTMs. We also highlight emerging strategies for the molecular targeting of epigenetic mechanisms with so-called “epidrugs” in HCC treatment and prevention.…”

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

“…The advances made in genome sequencing achieved over the past decades revealed that potentially between 97 and 98% of the human genome is transcribed into ncRNAs, which do not code for proteins but are somewhat involved in DNA replication, RNA splicing, translation, and epigenetic regulation of various biological processes, including hepatocarcinogenesis [ 99 ]. Based on their sequence length, these noncoding transcripts are divided into two groups: short ncRNAs containing less than ~200 nucleotides and long noncoding RNAs exceeding this threshold.…”

Host Epigenetic Alterations and Hepatitis B Virus-Associated Hepatocellular Carcinoma

“…Alterations appear to be more frequent in lysine MTs (KMTs) and lysine MDs (KDMs) than in HATs or BRD proteins [ 24 ]. The increasing knowledge about the epigenetic mechanisms involved in liver carcinogenesis (for recent reviews see [ 25 , 26 , 27 , 28 ]) ( Figure 2 ) opens perspectives for novel therapeutic approaches for HCC treatment.…”