MicroRNA Profiling in Patients with Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy

Abstract

Balkan endemic nephropathy (BEN) is a disease that affects people that live in the alluvial plains along the tributaries of the Danube River in the Balkan region. BEN is a chronic tubulointerstitial disease with a slow progression to terminal renal failure and has strong association with upper tract urothelial carcinoma (UTUC). There are several hypotheses about the etiology of BEN, but only the toxic effect of aristolochic acid has been confirmed as a risk factor in the occurrence of the disease. Aberrantly expressed miRNAs have been shown to be associated with many types of cancers. A number of studies have investigated the expression of microRNAs in urothelial carcinoma, mainly on urothelial bladder cancer, and only a few have included patients with UTUC. Here we present the first study of microRNA profiling in UTUC tissues from patients with BEN (BEN-UTUC) and patients with UTUC from nonendemic Balkan regions (non-BEN-UTUC) in comparison to normal kidney tissues. We found 10 miRNAs that were differentially expressed in patients with BEN-UTUC and 15 miRNAs in patients with non-BEN-UTUC. miRNA signature determined in BEN-UTUC patients differs from the non-BEN-UTUC patients; only miR-205-5p was mutual in both groups.

Integration of medicinal plants into the traditional system of medicine for the treatment of cancer in Sokoto State, Nigeria

“…Generally, Aristolochia and one of its chief components aristolochic acid have been known for its carcinogenic, and nephrotoxic effects for a very long time ( Michael et al., 2009 ). Recently, several toxicological risks associated with a history of using herbal medicines containing aristolochic acid amongst cancer patients have been reported ( Aydin et al., 2017 ; Ban et al., 2018 ; Chen et al., 2018 ; Hoang et al., 2016 ; Hung et al., 2016 ; Kanaan et al., 2016 ; Popovska-Jankovic et al., 2016 ; Xiong et al., 2018 ; Zhong et al., 2017 ). Despite the reported cases on the use of herbs containing aristolochic acid around the world, a similar effect associated with the use of Aristolochia spp has yet to be reported in Nigeria.…”

Molecular Characterization of Upper Tract Urothelial Carcinoma in the Era of Next-generation Sequencing: A Systematic Review of the Current Literature

“…Tao et al [47] reported a serum signature comprising 10 miRNAs to potentially distinguish UTUC from healthy patients with hematuria, and Zaravinos et al [48] analyzed miRNA expression profiles to distinguish renal cell carcinoma and UTUC samples from each other and from healthy tissue. One study focused on biological pathways affected by differential miRNA expression [49], and two studies particularly analyzed miRNAs involved in AAinduced UTUC [50,51]. It is noteworthy that AA-induced UTUC was reported to harbor different miRNA signatures compared with sporadic UTUC.…”

Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinogenicity, and Underlying Mechanisms

“…In recent years, more than 30 microRNAs differentially expressed in patients exposed to AAs have been explored, which might improve the understanding of the pathogenesis of AA-related renal disease and cancer. It has been speculated that FGFR3, Akt, mucin type O-glycan biosynthesis, ECM receptor interaction pathways, and other biological mechanisms might be involved in the occurrences of AAN, BEN, and/or AA-induced UTUC (Tao et al, 2015; Lv et al, 2016; Popovska-Jankovic et al, 2016). Meanwhile, 15% of the 417 detectable miRNAs have been found to be altered by AAs in rats (Li et al, 2015).…”