Overexpression of miR-21-5p in colorectal cancer cells promotes self-assembly of E-cadherin-dependent multicellular tumor spheroids. (August 2020)

• Record Type: Journal Article
• Authors: Li, Albert; Yang, Pei-Ming
• Is Part Of: Tissue & cell. Volume 65(2020)
• Publication Date: 2020-08
• Subjects: 2D two-dimensional -- 3D three-dimensional -- 5-FU 5-fluorouracil -- CRC colorectal cancer -- CTC circulating tumor cells -- FBS fetal bovine serum -- MCTS multicellular tumor spheroid -- miRNA microRNA -- PCR polymerase chain reaction; Colorectal cancer -- microRNA -- Multicellular tumor spheroid -- Cell-cell adhesion; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2020.101365
• Languages: English
• ISSNs: 0040-8166

Abstract

Highlights: Overexpression of miR-21−5p in colorectal cancer promotes multicellular tumor spheroids (MCTS). Culturing miR-21−5p-overexpressing colorectal cancer in suspension is sufficient to induce MCTS formation. miR-21−5p-mediated MCTS formation is E-cadherin-dependent. 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.