A novel messenger RNA and long noncoding RNA signature associated with the progression of nonmuscle invasive bladder cancer

摘要

Abstract Aim To explore the molecular mechanism of nonmuscle invasive bladder cancer (NMIBC), matched normal, and cancer tissues of 10 NMIBC were examined for RNA sequencing. Methods We profiled the messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression of patients with NMIBC. Differentially expressed mRNAs and lncRNAs were screened between cancer and normal tissues and validated by quantitative polymerase chain reaction (qPCR), and lncRNA‐mRNA‐miRNA interaction network was constructed. Results A total of 91 upregulated and 190 downregulated genes and 34 upregulated and 58 downregulated lncRNAs were screened from the sequencing result. The differentially expressed mRNAs were enriched in focal adhesion, rap1 signaling pathway, Hippo signaling pathway, PI3K‐Akt signaling pathway, extracellular matrix (ECM)‐receptor interaction, Ras signaling pathway, and mitogen‐activated protein kinases signaling pathway, of which some pathways were involved in the cancer development. In the RNA sequencing, KIT and laminin subunitγ γ3 (LAMC3) were significantly downregulated in the NMIBC group compared with the normal group. The results of quantitative reverse transcription PCR showed that the expression of LAMC3 and KIT were significantly decreased in the NMIBC group compared with the normal group. The lncRNA‐mRNA‐miRNA interaction network was constructed by Cytoscape software to further investigate the interaction correlations. The results implied that KIT and LAMC3 might regulate the lncRNAs (such as ENST00000445707, ENST00000501122, ENST00000505254, ENST00000528986, ENST00000557661, ENST00000602964, ENST00000614517, ENST00000620864, and ENST00000623414) by the miRNAs (such as hsa‐let‐7f‐2‐3p, hsa‐miR‐125a‐3p, hsa‐miR‐134‐3p, hsa‐miR‐191‐5p, hsa‐miR‐210‐5p, hsa‐miR‐30a‐5p, hsa‐miR‐30d‐5p, hsa‐miR‐30e‐5p, hsa‐miR‐92a‐2‐5p, and hsa‐miR‐95‐3p), and finally played a role in the development of NMIBC cancer. Conclusion Altogether, our study preliminarily indicated that KIT and LAMC3 might play a crucial role in the development of NMIBC cancer via a complex mRNA‐lncRNA‐miRNA regulatory network.