Gene expression profiling and construction of a putative gene regulatory network of bladder cancer tumor-initiating cells

// Zhuoyuan Xin 1, 2, * , Zhao Yang 3, * , Jianting Xu 1, ** , Chaoying Li 2 , Tong Shao 2 , Guoqing Wang 2 and Chong Li 3, 4 1 Cancer Centre, First Hospital of Jilin University, Changchun, China 2 Department of Pathogenobiology, College of Basic Medical Science, Jilin University, Changchun, China 3 Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 4 Beijing Jianlan Institute of Medicine, Beijing, China * These authors contributed equally to this work ** Co-author Correspondence to: Chong Li, email: lichong@moon.ibp.ac.cn Guoqing Wang, email: qing@jlu.edu.cn Keywords: bladder cancer; gene expression profile; tumor-initiating cells; stem-like cells; gene regulatory network Received: August 24, 2017     Accepted: September 22, 2017     Published: November 30, 2017 ABSTRACT Human bladder cancer tumors have been shown to contain a subpopulation of cells with stem-like characteristics that may trigger tumor growth, recurrence, and metastasis. These cells, known as tumor-initiating cells (TICs), would be effective diagnostic tools and valuable therapeutic targets. Here, we report the isolation of TICs from seven bladder cancer cell lines and show that TICs from different sources vary on their ability to form tumorspheres in vitro and generate xenografts in vivo , which suggest they are remarkably heterogeneous. We used the Affymetrix PrimeView TM Human Gene Expression Array to analyze gene expression profiles of bladder TICs, which may help understand their tumorigenic capacities and develop novel treatments specifically targeted toward these cells. We then constructed a transcription factor-gene regulatory network that includes three key transcription factors that are involved in cell survival, differentiation, proliferation, and apoptosis. We validated our findings by analyzing mRNA expression of the key genes in this network in 24 clinical tissues. Our results suggest that this transcription factor-gene regulatory network could be useful in the development of clinical diagnostic tools and therapy approaches for bladder cancer.