Identification of differentially expressed miRNAs and miRNA-targeted genes in bladder cancer

// Jong-Young Lee 1, 9, 10, * , Seok Joong Yun 2, * , Pildu Jeong 2 , Xuan-Mei Piao 2 , Ye-Hwan Kim 2 , Jihye Kim 9 , Sathiyamoorthy Subramaniyam 9 , Young Joon Byun 2 , Ho Won Kang 2 , Sung Phil Seo 2 , Jayoung Kim 3 , Jung Min Kim 4 , Eun Sang Yoo 5 , Isaac Y. Kim 6 , Sung-Kwon Moon 7 , Yung Hyun Choi 8 and Wun-Jae Kim 2 1 Department of Business Data Convergence, Chungbuk National University, Cheongju, Republic of Korea 2 Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea 3 Department of Surgery, Department of Biomedical Sciences, Cedars-Sinai Medical Center, University of California Los Angeles, Los Angeles, California, USA 4 NAR Center, Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon, Republic of Korea 5 Department of Urology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea 6 Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA 7 Department of Food Science and Technology, Chung-Ang University, Ansung, Republic of Korea 8 Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, Republic of Korea 9 Microarray Division, Theragen Etex Bio Institute, Suwon, Republic of Korea 10 Microarray Division, SNP Medicine Co., Ltd, Suwon, Republic of Korea * These authors made an equal contribution to this article Correspondence to: Wun-Jae Kim, email: wjkim@chungbuk.ac.kr Keywords: bladder cancer tumorigenesis; miRNA; mRNA; miRNA-mRNA interaction; transcription factor Received: January 31, 2017      Accepted: August 28, 2017      Epub: February 07, 2018      Published: June 12, 2018 ABSTRACT Background : Differentially expressed genes and their post-transcriptional regulator-microRNAs (miRNAs), are potential keys to pioneering cancer diagnosis and treatment. The aim of this study was to investigate how the miRNA-mRNA interactions might affect the tumorigenesis of bladder cancer (BC) and to identify specific miRNA and mRNA genetic markers in the two BC types: non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). Results : We identified 227 genes that interacted with 54 miRNAs in NMIBC, and 14 genes that interacted with 10 miRNAs in MIBC. Based on this data, we found extracellular matrix-related genes are highly enriched in NMIBC while genes related to core nuclear division are highly enriched in MIBC. Furthermore, using a transcriptional regulatory element database, we found indirect regulatory transcription factors (TFs) for enriched genes could regulate tumorigenesis with or without miRNAs. Materials and methods : Tissue samples from 234 patients histologically diagnosed with BC and 83 individuals without BC were analyzed using microarray and next-generation sequencing technology, and we used different cut-offs to identify differentially expressed mRNAs and miRNAs in NMIBC and MIBC. The selected mRNAs and miRNAs were paired using validated target datasets and according to inverse expression relationships. MiRNA interacted genes were compared with the TF-regulating genes in BC. Meanwhile, pathway enrichment analysis was performed to identify the functions of selected miRNAs and genes. Conclusions : Identification of differential gene expression in specific tumor types could facilitate development of cancer diagnosis and aid in the early detection of BC.