Molecular pathogenesis of interstitial cystitis based on microRNA expression signature: miR-320 family-regulated molecular pathways and targets

Interstitial cystitis (IC), also known as bladder pain syndrome, is a chronic inflammatory disease that affects the bladder. The symptoms of IC vary, including feeling an urgent need for immediate urination and of needing to urinate often, as well as bladder or pelvic pain. Despite its high incidence, no molecular diagnostic methods are available for IC, and the molecular pathogenesis is unknown. microRNAs (miRNA) can regulate expression of RNA transcripts in cells and aberrant expression of miRNAs is associated with several human diseases. Here, we investigated the molecular pathogenesis of IC based on miRNA expression signatures. RNA sequencing of miRNA levels in IC tissues and comparison with levels in normal bladder tissue and bladder cancer revealed dysregulated expression of 366 miRNAs (203 and 163 down- and upregulated miRNAs, respectively). In particular, miR-320 family miRNAs(miR-320a, miR-320b, miR-320c, miR-320d and miR-320e) had downregulated expression in IC tissues. Genome-wide gene expression analyses and in silico database analyses showed that three transcription factors, E2F-1, E2F-2 and TUB, are regulated by miR-320 family miRNAs. Immunostaining of IC tissues confirmed that these transcription factors are overexpressed in IC tissues. Novel approaches that identify aberrantly expressed miRNA regulatory networks in IC could provide new prognostic markers and therapeutic targets for this disease.

Journal of human genetics. 2018 Mar 12 [Epub ahead of print]

Takayuki Arai, Miki Fuse, Yusuke Goto, Kanya Kaga, Akira Kurozumi, Yasutaka Yamada, Sho Sugawara, Atsushi Okato, Tomohiko Ichikawa, Tomonori Yamanishi, Naohiko Seki

Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Urology, Continence Center, Dokkyo Medical University, Mibu, Tochigi, Japan., Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan. .

Pelvic Health Weekly Newsletter