DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1

Xin Sun, Shou-Ching Tang, Chongwen Xu, Chenguang Wang, Sida Qin, Ning Du, Jian Liu, Yiwen Zhang, Xiang Li, Gang Luo, Jie Zhou, Fei Xu, Hong Ren

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Let-7 miRNAs act as tumour suppressors by directly binding to the 3′UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback relationship is Dicer, a central regulator of miRNA expression through sequence-specific silencing. We first identified that DICER1 is the key downstream gene for cyclin D1-induced let-7 expression. In addition, we found that let-7 miRNAs expression decreased because of the p53-induced cell death response, with deregulated cyclin D1. Our results also showed that cyclin D1 is required for Nutlin-3 and TAX-induced let-7 expression in cancer repression and the cell death response. For the first time, we provide evidence that let-7 and cyclin D1 form a feedback loop in regulating therapy response of cancer cells and cancer stem cells, and importantly, that alteration of let-7 expression, mainly caused by cyclin D1, is a sensitive indicator for better chemotherapies response.

Original languageEnglish (US)
Pages (from-to)1357-1365
Number of pages9
JournalJournal of Cellular and Molecular Medicine
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • Cancer stem cells
  • Cell apoptosis
  • Cyclin D1
  • DICER1
  • Let-7
  • Regulatory loop

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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  • Cite this

    Sun, X., Tang, S-C., Xu, C., Wang, C., Qin, S., Du, N., Liu, J., Zhang, Y., Li, X., Luo, G., Zhou, J., Xu, F., & Ren, H. (2015). DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1. Journal of Cellular and Molecular Medicine, 19(6), 1357-1365. https://doi.org/10.1111/jcmm.12522