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Updated: May 27, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
08:40

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFβR2) in colon cancer

Yingjie Yu1, Shailender S Kanwar, Bhaumik B Patel

  • 1Department of Veterans Affairs Medical Center, Detroit, MI 48201, USA.

Carcinogenesis
|November 11, 2011
PubMed

Insights

MicroRNA-21 (miR-21) promotes colon cancer stemness by targeting TGFβR2, increasing stem cell traits and tumor growth. This study reveals miR-21

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-21 (miR-21) is implicated as an oncogene targeting tumor suppressor genes like PDCD4.
  • The role of miR-21 in cancer stem cells (CSCs) remains incompletely understood.

Purpose of the Study:

  • To elucidate the mechanism by which miR-21 influences cancer stem cell properties in colon cancer.
  • To identify direct targets of miR-21 involved in stemness regulation.

Main Methods:

  • Analysis of miR-21 and PDCD4 levels in FOLFOX-resistant colon cancer cells enriched in CSCs.
  • Overexpression of miR-21 in HCT-116 cells and assessment of downstream targets and CSC phenotypes.
  • Luciferase reporter assays to validate TGFβR2 as a direct miR-21 target.
  • In vitro sphere formation assays and in vivo tumor formation studies in SCID mice.

Main Results:

  • FOLFOX-resistant colon cancer cells exhibited increased miR-21 and decreased PDCD4.
  • miR-21 overexpression downregulated PDCD4 and TGFβR2, while enhancing β-catenin, TCF/LEF activity, c-Myc, and Cyclin-D expression.
  • Increased miR-21 promoted sphere formation and tumor growth in vivo.
  • TGFβR2 was identified as a direct target of miR-21, and its restoration attenuated miR-21-induced stemness markers.

Conclusions:

  • miR-21 promotes colon cancer stemness and tumor progression.
  • The mechanism involves the downregulation of TGFβR2 and subsequent modulation of the Wnt/β-catenin pathway.
  • miR-21 represents a potential therapeutic target for overcoming chemoresistance and targeting CSCs in colon cancer.

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