MicroRNA-720 Regulates E-cadherin–αE-catenin Complex and Promotes Renal Cell Carcinoma

Abstract

MicroRNAs are implicated in regulating cancer progression and metastasis. Here we show that miR-720 is positively associated with renal cell carcinoma (RCC). Elevated levels of miR-720 were observed in a panel of RCC cell lines and clinical tissues compared to non-malignant cell line and normal samples. Loss of miR-720 function inhibited proliferation, migration and invasion and induced apoptosis in RCC cell lines in vitro and repressed tumor growth in xenograft mouse model. Conversely, gain of miR-720 function in non-malignant HK-2 cells induced pro-cancerous characteristics. Silencing of miR-720 caused a marked induction in the levels of endogenous αE-catenin and E-cadherin protein levels in anti720 transfected cells compared to control. Whereas, miR-720 overexpression in RCC cell lines reduced activity of a luciferase reporter gene fused to the wild-type αE-catenin or E-cadherin 3′ UTR compared to non-specific 3′ UTR control indicating that αE-catenin-E-cadherin complex is a direct and functional target of miR-720 in RCC. We also observed attenuation of β-Catenin, CD44 and Akt expression in RCC cells transfected with miR-720 inhibitor compared to control. Further, miR-720 exhibited clinical significance in RCC. Expression of miR-720 significantly distinguished malignant from normal samples. Elevated miR-720 levels positively correlated with higher Fuhrman grade, pathological stage and poor overall survival of RCC patients. These findings uncover a new regulatory network in RCC involving metastasis-promoting miR-720 that directly targets expression of key metastasis-suppressing proteins E-cadherin and αE-catenin complex. These results suggest that therapeutic regulation of miR-720 may provide an opportunity to regulate EMT and metastasis in RCC.

Restoration of E-cadherin by PPBICA protects against cisplatin-induced acute kidney injury by attenuating inflammation and programmed cell death

“…In fact, evidence shows that reduced E-cadherin is correlated with β-catenin expression and poor prognosis of renal RCC; and, E-cadherin prevents β-catenin translocation from membrane to cytoplasm, suppressing wnt/β-catenin signaling [16]. A recent study showed that inhibition of E-cadherin-α/E-catenin complex by miR-720 promoted RCC [17], indicating a preventive role of E-cadherin in RCC. In the fibrotic kidney, loss of E-cadherin, which is a marker for epithelial cells, and gain of α-SMA expression, the marker for myofibroblasts, is a key process in myofibroblast transdifferentiation from epithelial origin [18].…”

miR-124 and miR-203 synergistically inactivate EMT pathway via coregulation of ZEB2 in clear cell renal cell carcinoma (ccRCC)

“…MicroRNAs (miRNAs) are master gene regulators that may silence genes at the post-transcriptional level via transcript degradation or translational repression. miRNAs are extensively implicated in fundamental biological processes and aberrant microRNA profiles have been reported in various cancers including RCC [3][4][5].…”

Identification of genomic copy number variations in lung benign metastasizing leiomyomatosis

“…In this study, six chromosomes presented CNVs involving genes encoding for proteins, miRNAs (short no‐coding RNAs conformed by 20‐25 nucleotides), or lncRNAs (long no‐coding RNAs constituted by ~200 nucleotides) involved in the regulation of gene expression. The potential of these both kind of RNAs to modulate gene expression is being extensively described . These molecules regulate gene expression finely, but their perturbed activity can disturb the normal genome behaviour and promote pathological conditions …”