Abstract 518: Dual strands of pre-miR-223 (miR-223-5p and miR-223-3p) possess antitumor roles and these are involved in bladder cancer pathogenesis

Abstract

Abstract Bladder cancer (BC) is a common urologic cancer and the ninth most common cause of death worldwide. In 2015, it was estimated that approximately 76,000 new cases were diagnosed as BC and 1600 patients died in United States of America. Approximately 70-80% of patients are diagnosed with non-muscle-invasive BC (NMIBC) at the first visit and high recurrence rates (50%-70%) are observed in this patients. Moreover, 15% of recurrent BC progress to muscle-invasive BC (MIBC) and 5-year survival rate for patients with MIBC is only approximately 60%. At present, there are no effective treatments for patients with advanced BC or failure of first-line treatment. MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules (19-22 bases in length) that act as fine-tuners for RNA expression in a sequence-specific manner. Unique nature of miRNA is a single miRNAs might be controlled a large number of protein-coding or protein noncoding RNAs in cells. Abnormal expression of miRNAs will be caused disruption of intracellular RNA networks and these events are involved in human diseases. In this study, we focused on both strands of pre-miR-223 (miR-223-5p and miR-223-3p) based on miRNA signature of bladder cancer (BC) and to investigate the functional significance of these miRNA in BC cells. Ectopic expression of these miRNAs showed that as in miR-223-3p (guide strand), miR-223-5p (passenger strand) inhibited the abilities of cancer cell migration and invasion in BC cells. Combination of gene expression and in silico database analyses demonstrated that a total of 33 putative targets were identified as miR-223-5p regulation in BC cells. Among these target genes, high expression of 5 genes (ANLN, HMMR, CDC20, GJB2 and BUB1B) were significantly associated with poor prognosis of the patients with BC by The Cancer Genome Atlas (TCGA) database analyses. Moreover, knockdown of ANLN significantly inhibited cell proliferation, migration, and invasion (P < 0.0001). The ANLN was highly expressed in BC clinical specimens. These results indicated that ANLN acts as an oncogene in BC. Aberrant expressed ANLN was detected in BC clinical specimens and its high expression was deeply involved in BC pathogenesis. Involvement of passenger strands of miRNAs in cancer pathogenesis is a novel concept of cancer research and novel miRNAs-mediated molecular networks may lead to a better understanding of BC pathogenesis and the development of new treatment protocols. Citation Format: Sho Sugawara, Yasutaka Yamada, Takayuki Arai, Atsushi Okato, Mayuko Kato, Tomohiko Ichikawa, Naohiko Seki. Dual strands of pre-miR-223 (miR-223-5p and miR-223-3p) possess antitumor roles and these are involved in bladder cancer pathogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 518.