MicroRNAs in Cholangiopathies

O’Hara, Steven P.; Gradilone, Sergio A.; Masyuk, Tetyana V.; Tabibian, James H.; LaRusso, Nicholas F.

doi:10.1007/s40139-014-0048-9

Cited by 27 publications

(22 citation statements)

References 86 publications

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“…The contribution of miRNAs in PLD pathogenesis was recently shown [66, 67]. MiRNA profiles are globally affected in cystic cholangiocytes with the majority of them being down-regulated.…”

Section: Therapeutic Targets In Pldmentioning

confidence: 99%

Therapeutic Targets in Polycystic Liver Disease

Masyuk

LaRusso

2017

CDT

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Polycystic liver diseases (PLD) are a group of genetic disorders initiated by mutations in several PLD-related genes and characterized by the presence of multiple cholangiocyte-derived hepatic cysts that progressively replace liver tissue. PLD co-exists with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Autosomal Recessive PKD as well as occurs alone (i.e., Autosomal Dominant Polycystic Liver Disease [ADPLD]). PLD associated with ADPKD and ARPKD belong to a group of disorders known as cholangiociliopathies since many disease-causative and disease-related proteins are expressed in primary cilia of cholangiocytes. Aberrant expression of these proteins in primary cilia affects their structures and functions promoting cystogenesis. Current medical therapies for PLD include symptomatic management and surgical interventions. To date, the only available drug treatment for PLD patients that halt disease progression and improve quality of life are somatostatin analogs. However, the modest clinical benefits, need for long-term maintenance therapy, and the high cost of treatment justify the necessity for more effective treatment options. Substantial evidence suggests that experimental manipulations with components of the signaling pathways that influence cyst development (e.g., cAMP, intracellular calcium, receptor tyrosine kinase, transient receptor potential cation channel subfamily V member 4 (TRPV4) channel, mechanistic target of rapamycin (mTOR), histone deacetylase (HDAC6), Cdc25A phosphatase, miRNAs and metalloproteinases) attenuate growth of hepatic cysts. Many of these targets have been evaluated in pre-clinical trials suggesting their value as potential new therapies. This review outlines the current clinical and preclinical treatment strategies for PLD.

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“…The contribution of miRNAs in PLD pathogenesis was recently shown [66, 67]. MiRNA profiles are globally affected in cystic cholangiocytes with the majority of them being down-regulated.…”

Section: Therapeutic Targets In Pldmentioning

confidence: 99%

Therapeutic Targets in Polycystic Liver Disease

Masyuk

LaRusso

2017

CDT

Self Cite

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“…Among these molecules, aberrant expression of miRNAs has received a great deal of attentions for its diagnostic and prognostic value in different kinds of human cancers, such as breast cancer, lung cancer, colorectal carcinoma, and hepatocellular cancer [32][33][34][35][36]. Steven et al [37] in summarizing recent studies on the role of miRNAs in CCA suggested that these miRNAs could be an important diagnostic and prognostic tool for CCA patients. Thus, the purpose of this study was to explore a novel functional miRNA for its value as a prognostic marker in CCA patients.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of miR-29a and Its Prognostic Significance in Patients with Cholangiocarcinoma

Deng

Chen²

2017

Oncol Res Treat

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Background: This study aimed to examine the expression level and prognostic value of microRNA-29a (miR-29a) in human cholangiocarcinoma (CCA). Patients and Methods: The expression of miR-29a was measured in tissues collected from 125 CCA patients using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Survival analysis was carried out using the Kaplan-Meier method and log-rank test. The prognostic value of miR-29a was examined with Cox regression analysis. Results: The results of qRT-PCR demonstrated that miR-29a expression was significantly upregulated in CCA tissue samples compared with matched noncancerous samples. Overexpression of miR-29a was found to be correlated with lymph node metastasis, clinical stage, and differentiation of CCA. The Kaplan-Meier survival curves suggested that patients with high miR-29a levels had poor overall survival compared to those with low miR-29a expression. From the results of the Cox regression analysis, we considered increased miR-29a expression to be an independent prognostic factor for patients with CCA. Conclusion: Our study data demonstrated that upregulated miR-29a expression is associated with progression of CCA and might act as a prognostic biomarker in CCA patients.

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“…Tissue engineering approaches mimicking biliary function would require a more complex microarchitecture of scaffolds that enable cell-cell interactions, allowing for biliary metabolism and transport [213,214]. Although little is known about the role of miRNAs in regulating cholangiocyte proliferation and function [215], several studies implicated specific miRNAs in the pathogenesis of cholangiocarcinoma. For example, the overexpression of miR-31 in cholangiocarcinoma cells altered RAS/MAPK signaling [216], and miR-138 can regulate cholangiocarcinoma proliferation, cell-cycle control, and migration, possibly by directly targeting RhoC [217].…”

Section: Liver Tissue Engineeringmentioning

confidence: 99%

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

Qian

Wang

et al. 2017

Engineering

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Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs (ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering. The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.

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MicroRNAs in Cholangiopathies

Cited by 27 publications

References 86 publications

Therapeutic Targets in Polycystic Liver Disease

Therapeutic Targets in Polycystic Liver Disease

Increased Expression of miR-29a and Its Prognostic Significance in Patients with Cholangiocarcinoma

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

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