Abstract
Bladder cancer stem cells (BCSCs), exhibiting self-renewal and differentiation capacities, may contribute to the tumor initiation, metastasis, recurrence and drug resistance of bladder cancer. However, the underlying functional mechanisms of BCSCs remain to be clarified. In this study, we describe the differentially-expressed mRNAs, lncRNAs, and circRNAs in BCSCs compared with that in bladder cancer non-stem cells (BCNSCs) through the transcriptome microarray data analysis using bladder cancer patients’ specimens. CircRNA_103809, the top one among the highly expressed circRNA identified in BCSCs, promotes the self-renewal, migration and invasion capabilities of bladder cancer by acting as a miR-511 sponge. Additionally, GO and KEGG pathway analysis suggest the differentially expressed genes identified may be involved in the cellular metabolism, differentiation and metastasis regulation of the cancer cells. Co-expression networks of lncRNAs/mRNAs and circRNAs/mRNAs constructed by WGCNA give a picture of the non-coding/coding RNAs regulating patterns in BCSCs. Notably, as core genes in the networks, AHCY, C6orf136 and LRIG1 show high potential to be prognosticators for bladder cancer. Therefore, further studies of non-coding RNA functional mechanisms in BCSCs is valuable for detecting the pathogenic mechanisms and discovering novel biomarkers in bladder cancer.
Highlights
Bladder cancer (BC) is one of the most life-threatening malignancies with high morbidity and mortality rates worldwide [1]
Compared with that in Bladder cancer non-stem cell (BCNSC), 1685 mRNAs, 1309 long non-coding RNA (lncRNA) and 113 circular RNA (circRNA) were highly expressed, while 1164 mRNAs, 1389 lncRNAs and 14 circRNAs were lowly expressed in Bladder cancer stem cell (BCSC)
We showed that the BCMab1+CD44+ cells act as bladder cancer stem cells (BCSCs) and are correlated with clinicalpathologic features of bladder cancer [31]
Summary
Bladder cancer (BC) is one of the most life-threatening malignancies with high morbidity and mortality rates worldwide [1]. Benefit from the continual development of neoplasm diagnosis and therapy methods, the death rate of cancer had been decreased in the past 10 years. Because of the lack of progress in the treatment for bladder cancer these years, the death rate of bladder cancer had barely changed [2]. Deeper researches on the pathogenesis and molecular biology of bladder cancer are needed to improve the diagnosis and treatment methods. The CSCs display the capacities of selfrenewal, differentiation and chemoresistance, which could affect the progression and recurrence of cancer significantly [7]. The molecular mechanisms underlying the stemness-like functions of bladder cancer stem cells (BCSCs), especially the genetic and epigenetic characters, remain largely elusive
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