MiR-26a-5p as a useful therapeutic target for upper tract urothelial carcinoma by regulating WNT5A/β-catenin signaling

Abstract

The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/β-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/β-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.

Genetic Interference of FGFR3 Impedes Invasion of Upper Tract Urothelial Carcinoma Cells by Alleviating RAS/MAPK Signal Activity

“…The TMA specimens were mainly collected from Caucasian patients diagnosed with either kidney pelvis UC ( n = 84) or ureteral UC ( n = 35). The human kidney cancer TMA and UTUC tissue slides were subjected to immunohistochemistry (IHC) staining as previously described [ 8 ], using an anti-FGFR3 antibody (Cat. No.…”

“…No. MK400, TaKaRa Bio Inc., Shiga, Japan) as previously described [ 8 , 9 ]. Cells grown on microtiter plates were treated with premixed WST-1 reagent for 4 h. The absorbance of a formazan end-product was measured at 440 nm and a reference wavelength at 600 nm using a microplate reader.…”

“…Protein concentrations were measured using a protein assay dye (Bio-Rad Laboratories, Hercules, CA, USA). SDS-PAGE and immunoblotting analyses were performed as described previously [ 8 , 9 , 50 ]. The detecting antibodies used for immunodetection are listed in Supplementary Table S1 .…”

“…The exposure gains and rates were consistent between the samples. The fluorescent intensities were quantified on independent color channels by using Image J software ver 1.48 (NIH, USA) [ 8 , 9 , 50 ].…”

“…Epithelial cells undergoing the EMT process may display the decreased expression of epithelial marker E-cadherin and conversely show the increased expression of transcription factors and mesenchymal markers, including vimentin, α-smooth muscle actin, and fibronectin. The increased expression of EMT markers has been found in UTUC tissues, and EMT markers are regarded as significant diagnostic and prognostic biomarkers [ 7 , 8 , 9 , 10 , 11 ]. Meanwhile, EMT induction with the concurrent degradation of the extracellular matrix (ECM), which facilitates tumor metastasis, is essential for the migration and invasion of cancer cells [ 9 , 10 , 11 , 12 , 13 , 14 ].…”