Pathogenetic Role and Clinical Implications of Regulatory RNAs in Biliary Tract Cancer

Abstract

Biliary tract cancer (BTC) is characterised by poor prognosis and low overall survival in patients. This is generally due to minimal understanding of its pathogenesis, late diagnosis and limited therapeutics in preventing or treating BTC patients. Non-coding RNA (ncRNA) are small RNAs (mRNA) that are not translated to proteins. ncRNAs were considered to be of no importance in the genome, but recent studies have shown they play essential roles in biology and oncology such as transcriptional repression and degradation, thus regulating mRNA transcriptomes. This has led to investigations into the role of ncRNAs in the pathogenesis of BTC, and their clinical implications. In this review, the mechanisms of action of ncRNA are discussed and the role of microRNAs in BTC is summarised. The scope of this review will be limited to miRNA as they have been shown to play the most significant roles in BTC progression. There is huge potential in miRNA-based biomarkers and therapeutics in BTC, but more studies, research and technological advancements are required before it can be translated into clinical practice for patients.

Keywords: LncRNA; biliary tract cancer; biomarker; miRNA; non-coding RNA; therapy.

Figure 1

A schematic illustration of miRNA biogenesis and mechanism of action. miRNA gene is transcribed by RNA polymerase II into primary miRNA (pri-miRNA). Pri-miRNAs are then processed in the nucleus by an enzyme named Drosha which has an RNAse III domain and a co-factor into miRNA precursors (pre-miRNAs). The pre-miRNAs are exported from the nucleus to the cytoplasm by Exportin-5 and co-factor RAN-GTP. The hairpin structure of pre-miRNA is cleaved off by Dicer to produce the miRNA duplex. RNA inducing silencing complex (RISC) binds with the long messenger RNA (mRNA) and can subsequently either repress or degrade mRNA.