Noncoding RNA-Based Therapeutic Approaches for Liver Diseases

As we know, the pervasive view of gene regulation in biology has been mostly concentrated in protein-coding genes via the central dogma of DNA → mRNA → protein. However, it has been well accepted that only less than 3% of genome sequences have the ability to encode protein, and at least 90% of the human genome is actively transcribed into noncoding RNAs (ncRNAs). In the past, ncRNAs were regarded as transcriptional “noise” or body “garbage”, which were supposed to have no biological functions. However, accumulating studies suggest that ncRNAs play an important role in the development of several diseases, especially in liver diseases. According to their size, ncRNAs are divided into two groups: small ncRNAs (<200 nucleotides) and long ncRNAs (>200 nucleotides). Over the past decade, microRNAs (miRNAs), which are endogenous small noncoding RNAs (~22 nucleotides) have been found to work at the posttranscriptional level to regulate gene expression by pairing with the 3’ untranslated region (3’ UTR) of target mRNA. There is overwhelming evidence that miRNAs are involved in the development and progression of several kinds of liver diseases, such as alcohol liver diseases (ALD), nonalcoholic fatty liver disease (NAFLD), liver fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Furthermore, miR-122 inhibitor has been tested in a phase 2a study for the treatment of hepatitis C. In addition, long noncoding RNAs (lncRNAs), which are commonly defined as endogenous cellular RNA molecules longer than 200 nucleotides in length, are poorly conserved and capable to govern fundamental biological processes at various levels, including chromosome dosage-compensation, imprinting, epigenetic regulation, nuclear and cytoplasmic trafficking, transcription, mRNA splicing and translation. Recently, the biological function of lncRNAs in liver diseases is attracting more attention. It has become increasingly obvious that several lncRNAs play a role in the progression of HCC and the development of liver fibrosis. However, little is known about the role of lncRNAs in other liver diseases.

The present Research Topic aims to give an overview of the most exciting progress in the field of noncoding RNAs in liver diseases. We believe that this Research Topic will give further insights in the biological of noncoding RNAs in liver diseases, which may act as prospective novel therapeutic targets for liver diseases.