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

19 Citations (Scopus)

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

Fingerprint

Cyclin D1
MicroRNAs
Neoplasms
Cell Death
Endoribonucleases
bcl-1 Genes
Neoplastic Stem Cells
Cell Cycle
Carcinogenesis
Gene Expression
Drug Therapy
Research
Genes

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1. / Sun, Xin; Tang, Shou-Ching; Xu, Chongwen; Wang, Chenguang; Qin, Sida; Du, Ning; Liu, Jian; Zhang, Yiwen; Li, Xiang; Luo, Gang; Zhou, Jie; Xu, Fei; Ren, Hong.

In: Journal of Cellular and Molecular Medicine, Vol. 19, No. 6, 01.06.2015, p. 1357-1365.

Research output: Contribution to journalArticle

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, vol. 19, no. 6, pp. 1357-1365. https://doi.org/10.1111/jcmm.12522
Sun, Xin ; Tang, Shou-Ching ; Xu, Chongwen ; Wang, Chenguang ; Qin, Sida ; Du, Ning ; Liu, Jian ; Zhang, Yiwen ; Li, Xiang ; Luo, Gang ; Zhou, Jie ; Xu, Fei ; Ren, Hong. / DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1. In: Journal of Cellular and Molecular Medicine. 2015 ; Vol. 19, No. 6. pp. 1357-1365.
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AU - Du, Ning

AU - Liu, Jian

AU - Zhang, Yiwen

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AB - 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.

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