Overexpression of miR-21-5p in colorectal cancer cells promotes self-assembly of E-cadherin-dependent multicellular tumor spheroids

Albert Li, Pei Ming Yang

Research output: Contribution to journalArticle

Abstract

Three-dimensional (3D) multicellular tumor spheroid (MCTS) cultures are increasingly popular as an in vitro tumor model for drug screening because they can mimic the complexity and heterogeneity of tumors compared to 2D monolayer cell cultures. The oncogenic microRNA, miR-21−5p (hereafter denoted as miR-21), is one of the most upregulated miRNAs in colorectal cancer (CRC). Herein, we established a stable miR-21-overexpressing clone in the DLD-1 human CRC cell line to investigate its impact on MCTS formation. We found that miR-21 overexpression enhanced cell-cell interactions/aggregations in both 2D monolayer and 3D suspension cultures. Cell aggregates in 3D suspension culture further formed MCTSs in miR-21-overexpressing cells. miR-21 overexpression was associated with the upregulation of proteins involved in E-cadherin-associated cell-cell adhesion. Furthermore, miR-21 induction of MCTSs could be reversed by the antibody-induced blockade of E-cadherin. Our results showed that miR-21 overexpression promoted MCTS formation through enhancing E-cadherin-dependent cell-cell interactions, which represents an advance in vitro model for investigating CRC biology.

Original languageEnglish
Article number101365
JournalTissue and Cell
Volume65
DOIs
Publication statusPublished - Aug 2020

Keywords

  • Cell-cell adhesion
  • Colorectal cancer
  • microRNA
  • Multicellular tumor spheroid

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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