Insight into microRNAs-Mediated Communication between Liver and Brain: A Possible Approach for Understanding Acute Liver Failure?

Abstract

Acute liver failure (ALF) is a life-threatening consequence of hepatic function rapid loss without preexisting liver disease. ALF may result in a spectrum of neuropsychiatric symptoms that encompasses cognitive impairment, coma, and often death, collectively defined as acute hepatic encephalopathy (HE). Micro RNAs are small non-coding RNAs that modulate gene expression and are extensively verified as biomarker candidates in various diseases. Our systematic literature review based on the last decade’s reports involving a total of 852 ALF patients, determined 205 altered circulating miRNAs, of which 25 miRNAs were altered in the blood, regardless of study design and methodology. Selected 25 miRNAs, emerging predominantly from the analyses of samples obtained from acetaminophen overdosed patients, represent the most promising biomarker candidates for a diagnostic panel for symptomatic ALF. We discussed the role of selected miRNAs in the context of tissue-specific origin and its possible regulatory role for molecular pathways involved in blood–brain barrier function. The defined several common pathways for 15 differently altered miRNAs were relevant to cellular community processes, indicating loss of intercellular, structural, and functional components, which may result in blood-brain barrier impairment and brain dysfunction. However, a causational relationship between circulating miRNAs differential expression, and particular clinical features of ALF, has to be demonstrated in a further study.

Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer

“…This analysis revealed a total of 274 genes with significant differences in expression, including Several studies have shown that the deficiency of gap junction activity, which is influenced by the levels of connexins and tubulins, contributes to the resistance to chemotherapeutic agents, such as cisplatin, in various cancers, such as breast, colorectal, and lung. [19][20][21][22][23][24] F I G U R E 3 Gene Ontology (GO) of DEGs. The gene ontology of differentially expressed genes (DEGs) reveals the top 20 terms in three categories: biological process (BP), molecular function (MF), and cellular component (CC).…”

“…Several studies have shown that the deficiency of gap junction activity, which is influenced by the levels of connexins and tubulins, contributes to the resistance to chemotherapeutic agents, such as cisplatin, in various cancers, such as breast, colorectal, and lung. 19 , 20 , 21 , 22 , 23 , 24 …”

miRNA-ome plasma analysis unveils changes in blood–brain barrier integrity associated with acute liver failure in rats

“…Increasing evidence points to miR expression changes in body fluids and tissues from both HE patients [ 11 , 48 – 51 ] and animal models [ 52 – 56 ] but only a few studies used NGS or other large-scale methods showing whole miRNome changes [ 57 , 58 ].…”

“…MiRs, small non-coding RNA sequences, can negatively regulate protein levels by suppressing gene expression. Emerging evidence has suggested circulating non-coding RNAs’ diagnostic and therapeutic values in pathologies linked with liver diseases, including ALF [ 10 , 11 ]. Various miRs were recently proposed as possible biomarkers and regulatory factors in numerous CNS disorders expanding miRs’ contributing role in the control of the functioning of BBB-composing endothelial cells [ 12 – 14 ].…”

Clinical validation of miRNA biomarkers to predict risk of primary non-function of fatty allografts following liver transplantation

“…In general, miRNAs are small noncoding RNAs (21-23nt) and confer translational repression [15,16]. Their role as transcriptional regulators in liver diseases is a hot topic [17][18][19], and miRNAs are of critical importance in the regulation of hepatic lipid synthesis and metabolism [20]. Correspondingly, their contribution to the pathophysiology of fatty liver disease is the subject of intense research [21,22], and miRNA biomarkers carry the potential to assist in an evaluation of the quality of donor allografts [23].…”