LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis

Abstract

Background Alcoholic liver disease (ALD) is one of the leading causes of chronic liver disease. Recent studies have demonstrated the roles of long noncoding RNAs (lncRNAs) in the pathogenesis of several disease processes. However, the roles of lncRNAs in patients with ALD remain unexplored. Methods Global profiling for human lncRNAs from peripheral blood RNA was performed in a well characterized cohort of healthy controls (HC, n=4), excessive drinkers without liver diseases (ED, n=4), and those with alcoholic cirrhosis with different severities (AC, n=12). The expression of unique lncRNA signatures were validated in a separate cohort of HC (n=17), ED (n=19), AC (n=48), and human liver tissues with ALD (n=19). Results Detailed analysis of plasma lncRNAs in AC subjects with different severities compared to HC identified 244 commonly up-regulated lncRNAs and 181 commonly down-regulated lncRNAs. We further validated top 20 most differentially up- and down-regulated lncRNAs in ED and AC as compared to HC and also determined the expression of selected lncRNAs in human liver tissues with or without AC. Among those lncRNAs, AK128652 and AK054921 were two of the most abundantly expressed lncRNAs in normal human plasma and liver, and their levels were significantly elevated in AC. The prognostic significance of AK128652 and AK054921 was determined in 48 subjects with AC; who were prospectively followed for 520 days. The expression of AK128652 and AK054921 was inversely associated with survival in patients with AC. Conclusions LncRNAs AK054921 and AK128652 are potential biomarkers to predict the progression to ALD in those with excessive alcohol consumption and are predictors of survival with patients with alcoholic cirrhosis.

Decoding the role of extracellular vesicles in liver diseases

“…Recent studies also suggest the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of ALD. Yang et al 71 showed that lncRNAs, AK054921 and AK128652, are the two most abundantly expressed lncRNAs in normal human liver and that their levels were significantly elevated during ALD progression, indicating these two lncRNAs as novel candidates for ALD biomarkers. Whether these lncRNAs are released as EV cargos is still questionable.…”

Long non-coding RNA in liver metabolism and disease: Current status

“…5 The microRNAs (miRNAs) comprise a class of short single- stranded non-coding RNAs that regulate gene expression mainly through post-transcriptional regulation by binding to the 3′UTRs of target mRNAs. For example, a new study demonstrated that miR-127 modulates the pluripotency of liver tumor initiating cells by targeting HMGB2.…”

“…3 Extensive studies have been conducted on miRNAs, however the functions of lncRNAs remain poorly understood. 4,5 Recent studies have revealed that lncRNAs significantly impact on various biological processes as X-inactivation, genomic imprinting, chromatin modification, cell fate specification, cell apoptosis, nuclear trafficking, and genome rearrangement. 6 …”

Noninvasive diagnosis in alcohol‐related liver disease

“…They have also identified Heat shock protein 90 in ALD‐EVs as a mediator of macrophage activation. On the other hand, among transcriptomic approaches based on circulating small noncoding RNA (miRNA) and long‐noncoding RNAs (lncRNAs), several exosome‐associated miRNAs have been studied as potential biomarkers in preclinical studies . Briefly, in mouse models of ALD, serum levels of miR‐155 and miR‐122 were increased and, interestingly, enriched in circulating exosomes as well as miR‐192 and miR‐30a .…”