Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies

Abstract

Long non-coding RNAs (lncRNAs) are RNAs with lengths exceeding 200 nucleotides that are not translated into proteins. It is well-known that small non-coding RNAs, such as microRNAs (miRNAs), regulate gene expression and play an important role in cholangiopathies. Recent studies have demonstrated that lncRNAs may also play a key role in the pathophysiology of cholangiopathies. Patients with cholangiopathies often develop cholangiocarcinoma (CCA), which is cholangiocyte-derived cancer, in the later stage. Cholangiocytes are a primary target of therapies for cholangiopathies and CCA development. Previous studies have demonstrated that expression levels of lncRNAs are altered in the liver of cholangiopathies or CCA tissues. Some lncRNAs regulate gene expression by inhibiting functions of miRNAs leading to diseased liver conditions or CCA progression, suggesting that lncRNAs could be a novel therapeutic target for those disorders. This review summarizes current understandings of functional roles of lncRNAs in cholangiopathies and seek their potentials for novel therapies.

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype

“…Up to date, accumulating evidences have suggested that miRNAs play important roles and might be regarded as a potential therapeutic target in regulating the progression and development of several liver diseases (13)(14)(15)(16). Previous reports have demonstrated that there were increased levels of miR-130a-3p in myocardial injury, and downregulation of miR-130a-3p could remarkably relieve hypoxia-induced inflammation and inhibit the expression of fibrosis-related protein (17).…”

Long Non-Coding RNAs in Biliary Tract Cancer—An Up-to-Date Review

“…In this regard, Li et al could demonstrate an upregulation of the oncogenic lncRNA H19 in exosomes derived from cholangiocytes under pathological conditions in the bile acid, which demonstrates the possibility to use lncRNAs as biomarkers also in BTC [252]. A possible future therapeutic strategy for BTC might include the use of RNA interference substances against tumor-promoting lncRNAs or proteins that are essential for the lncRNA function [253,254]. The substance Patisiran represents a FDA-approved RNA-interfering treatment option for hereditary transthyretin amyloidosis and it will be interesting to see whether this concept can be translated into cancer research and RNA interfering drugs might be able to inhibit oncogenic lncRNAs [255].…”

“…The substance Patisiran represents a FDA-approved RNA-interfering treatment option for hereditary transthyretin amyloidosis and it will be interesting to see whether this concept can be translated into cancer research and RNA interfering drugs might be able to inhibit oncogenic lncRNAs [255]. On the contrary, the induction of tumor-suppressive lncRNAs might also represent a potential strategy against BTC [254]. As summarized in this review, lncRNAs are aberrantly expressed in BTC patient samples and are involved in diverse oncogenic processes in BTC.…”

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

“…Numerous abnormally expressing miRNAs are associated with HCC initiation and progression [ 76 , 77 ]. Various studies have exposed the biological roles of lncRNAs as regulators of transcription, modulators of mRNA processing, and organizers of nuclear domains [ 76 , 77 , 78 , 79 ]. Compared with linear RNAs, circRNAs are more stable to exonuclease and ribonuclease, with conserved structure and stable sequence and tissue specificity [ 78 , 79 ].…”