MiR-193b Mediates CEBPD-Induced Cisplatin Sensitization Through Targeting ETS1 and Cyclin D1 in Human Urothelial Carcinoma Cells

Siao Ren Lin, Hsin Chih Yeh, Wei Jan Wang, Hung Lung Ke, Hui Hui Lin, Wei Chi Hsu, Shih Yi Chao, Tzyh Chyuan Hour, Wen Jeng Wu, Yeong Shiau Pu, A. Mei Huang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) plays multiple roles in tumor progression. Studies have demonstrated that cisplatin (CDDP) induced CEBPD expression and had led to chemotherapeutic drug resistance. However, the underlying molecular mechanisms of CDDP-regulated CEBPD expression and its relevant roles in CDDP responses remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Abnormal miRNAs expression is associated with tumor progression. In current study, a large-scale PCR-based miRNA screening was performed to identify CEBPD-associated miRNAs in urothelial carcinoma cell line NTUB1. Eleven miRNAs were selected with more than twofold changes. MiR-193b-3p, a known tumor suppressor, down-regulated proto-oncogenes Cyclin D1, and ETS1 expression and led to cell cycle arrest, cell invasion, and migration inhibition. The expression of miR-193b-3p was associated with the DNA binding ability of CEBPD in CDDP response. CEBPD knocking-down approach provided a strong evidence of the positive correlation between CEBPD and miR-193b-3p. CDDP-induced CEBPD trans-activated miR-193b-3p expression and it directly targeted the 3′-UTR of Cyclin D1 and ETS1 mRNA, and silenced the protein expression. In addition, miR-193b-3p also inhibited cell migration activity, arrested cell at G1 phase, and sensitized NTUB1 to CDDP treatment. In conclusion, this study indicates that CEBPD exhibits an anti-tumorigenic function through transcriptionally activating miR-193b-3p expression upon CDDP treatment. This study provides a new direction for managing human urothelial carcinoma. J. Cell. Biochem. 118: 1563–1573, 2017.

Original languageEnglish (US)
Pages (from-to)1563-1573
Number of pages11
JournalJournal of Cellular Biochemistry
Volume118
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Keywords

  • CELL CYCLE
  • CHEMOTHERAPEUTIC DRUGS
  • MIGRATION
  • MicroRNA-193b-3p
  • TRANSCRIPTION FACTOR
  • UROTHELIAL CARCINOMA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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