Related Experiment Video
Updated: Mar 7, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting ADAM9 and TGFBR2
Jasmijn G M van Kampen1, Onno van Hooij1, Cornelius F Jansen1
1Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, the Netherlands.
Abstract:
Reversing epithelial-to-mesenchymal transition (EMT) in cancer cells has been widely considered as an approach to combat cancer progression and therapeutic resistance, but a limited number of broadly comprehensive investigations of miRNAs involved in this process have been conducted. In this study, we screened a library of 1120 miRNA for their ability to transcriptionally activate the E-cadherin gene CDH1 in a promoter reporter assay as a measure of EMT reversal. By this approach, we defined miR-520f as a novel EMT-reversing miRNA. miR-520f expression was sufficient to restore endogenous levels of E-cadherin in cancer cell lines exhibiting strong or intermediate mesenchymal phenotypes. In parallel, miR-520f inhibited invasive behavior in multiple cancer cell systems and reduced metastasis in an experimental mouse model of lung metastasis. Mechanistically, miR-520f inhibited tumor cell invasion by directly targeting ADAM9, the TGFβ receptor TGFBR2 and the EMT inducers ZEB1, ZEB2, and the snail transcriptional repressor SNAI2, each crucial factors in mediating EMT. Collectively, our results show that miR-520f exerts anti-invasive and antimetastatic effects in vitro and in vivo, warranting further study in clinical settings. Cancer Res; 77(8); 2008-17. ©2017 AACR.
Insights
MicroRNAs can reverse cancer cell changes. Researchers found miR-520f reverses epithelial-to-mesenchymal transition (EMT), inhibiting cancer invasion and metastasis in cell models and mice.
Area of Science:
- Molecular biology
- Cancer research
- Genetics
Background:
- Epithelial-to-mesenchymal transition (EMT) reversal is a promising strategy against cancer progression and drug resistance.
- Comprehensive investigations into microRNAs (miRNAs) regulating EMT are limited.
Purpose of the Study:
- To screen for miRNAs capable of reversing EMT by activating E-cadherin (CDH1) transcription.
- To define novel miRNAs involved in EMT reversal and assess their therapeutic potential.
Main Methods:
- A library of 1120 miRNAs was screened using a promoter reporter assay to identify EMT-reversing candidates.
- miR-520f expression was analyzed in cancer cell lines and its effects on invasion and metastasis were evaluated in vitro and in vivo.
- Mechanistic studies identified direct targets of miR-520f involved in EMT regulation.
Main Results:
- miR-520f was identified as a novel miRNA that reverses EMT by restoring E-cadherin levels.
- miR-520f suppressed cancer cell invasion and reduced lung metastasis in a mouse model.
- miR-520f directly targets ADAM9, TGFBR2, ZEB1, ZEB2, and SNAI2, key mediators of EMT.
Conclusions:
- miR-520f demonstrates significant anti-invasive and antimetastatic properties.
- These findings highlight miR-520f as a potential therapeutic agent for cancer, meriting further clinical investigation.
Related Concept Videos
01:16TGF - β Signaling Pathway
01:22MicroRNAs