A role for microRNA in cystic liver and kidney diseases

Abstract

The polycystic liver and kidney diseases are a family of disorders with heterogeneous etiologies. Proposed mechanisms of disease include ciliary dysfunction, excess cell proliferation, and altered cell-cell or cell-matrix interactions. In this issue of the JCI, Lee and colleagues provide data to support a novel mechanism for cystogenesis involving microRNA (miRNA) (see the related article beginning on page 3714). They demonstrate that levels of the miRNA miR15a are decreased in livers of patients with autosomal recessive and autosomal dominant polycystic kidney disease (ARPKD and ADPKD, respectively) and congenital hepatic fibrosis as well as in the PKC rat model of ARPKD. This results in increased expression of the cell-cycle regulator Cdc25A, which is a direct target of miR15a, and increased cellular proliferation and cystogenesis in vitro. These findings suggest that other miRNAs may also participate in the molecular pathogenesis of cystic liver and kidney diseases.

MicroRNA signatures in liver diseases

“…This results in increased expression of the cell-cycle regulator Cdc25A, which is a direct target of miR15a, and increased cellular proliferation and cystogenesis in vitro. As a whole, the findings indicate that changes in miRNA expression contribute to the phenotypic changes found in cystic liver disease (Figure 3) [49,50] . miRNAS fOR ThE DIAGNOSIS Of LIvER DISEASES miRNAs could be of diagnostic significance for many liver diseases but current literature has been focused on tumors in the liver.…”

“…Autosomal dominant polycystic kidney disease (ADPKD) is associated with renal and liver cystogenesis that clinically manifests in adulthood, often leading to dialysis and renal transplantation. It is caused by mutations in either of two genes, PKD1 and PKD2, which code for polycystin 1 and polycystin 2, respectively [49] . Autosomal recessive polycystic kidney disease (ARPKD) can present in neonates with massive renal cysts, causing respiratory failure secondary to abdominal competition that subsequently leads to infant demise, although milder forms can present later in life.…”

“…Reduction of miR15a results in elevated Cdc25A level, increased cell proliferation, and cyst growth. This figure is reprinted from Chu and Friedman [49] with the permission of the authors and the publisher. in their clinical behavior and prognosis.…”

Mini-review: emerging roles of microRNAs in the pathophysiology of renal diseases

“…The inherited mutations are frequently observed within specific genes, including PKD1, PKD2, and PKHD1, which contribute to abnormal proliferation resulting in cyst formation (19). Recent studies with global miRNA profiling have shown that the miRNA expression pattern is significantly altered in PKD models, suggesting that miRNAs may act as disease modulators downstream of PKD mutations (25,108). In an interesting study (112), it was shown that the miR-17ϳ92 cluster is upregulated in mouse models of PKD.…”

Effects of MicroRNA-106 on Proliferation of Gastric Cancer Cell through Regulating p21 and E2F5

“…A lot of specific miRNAs differentially expressed in gastric cancer and normal gastric mucosa, such as miR-21, miR-34b/c, miR-221/222 and miR-106a is highly expressed in gastric cancer, compared with low expression of miR-124a, miR128b, miR-148 and miR-129 (Konishi et al, 2012;Li et al, 2012). Murakami found that miR-222, miR-106a, miR-92, miR-17-5p, miR-20 and miR-18 are related to the degree of differentiation, indicating that specific miRNAs and disease processes (Chu et al, 2008).…”