Affordable Access

Access to the full text

Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer

Authors
  • Nwaeburu, Clifford C.1
  • Abukiwan, Alia1
  • Zhao, Zhefu1
  • Herr, Ingrid1
  • 1 University of Heidelberg, Department of General, Molecular OncoSurgery, Section Surgical Research, Visceral and Transplantation Surgery, Im Neuenheimer Feld 365, Heidelberg, 69120, Germany , Heidelberg (Germany)
Type
Published Article
Journal
Molecular Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jan 31, 2017
Volume
16
Issue
1
Identifiers
DOI: 10.1186/s12943-017-0589-8
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundCancer stem cells are suggested to contribute to the extremely poor prognosis of pancreatic ductal adenocarcinoma and dysregulation of symmetric and asymmetric stem cell division may be involved. Anticancer benefits of phytochemicals like the polyphenol quercetin, present in many fruits, nuts and vegetables, could be expedited by microRNAs, which orchestrate cell-fate decisions and tissue homeostasis. The mechanisms regulating the division mode of cancer stem cells in relation to phytochemical-induced microRNAs are poorly understood.MethodsPatient-derived pancreas tissue and 3 established pancreatic cancer cell lines were examined by immunofluorescence and time-lapse microscopy, microRNA microarray analysis, bioinformatics and computational analysis, qRT-PCR, Western blot analysis, self-renewal and differentiation assays.ResultsWe show that symmetric and asymmetric division occurred in patient tissues and in vitro, whereas symmetric divisions were more extensive. By microarray analysis, bioinformatics prediction and qRT-PCR, we identified and validated quercetin-induced microRNAs involved in Notch signaling/cell-fate determination. Further computational analysis distinguished miR-200b-3p as strong candidate for cell-fate determinant. Mechanistically, miR-200b-3p switched symmetric to asymmetric cell division by reversing the Notch/Numb ratio, inhibition of the self-renewal and activation of the potential to differentiate to adipocytes, osteocytes and chondrocytes. Low miR-200b-3p levels fostered Notch signaling and promoted daughter cells to become symmetric while high miR-200b-3p levels lessened Notch signaling and promoted daughter cells to become asymmetric.ConclusionsOur findings provide a better understanding of the cross talk between phytochemicals, microRNAs and Notch signaling in the regulation of self-renewing cancer stem cell divisions.

Report this publication

Statistics

Seen <100 times