A protein-mRNA feedback exists in miR-21-associated E-selectin expression

Area of Science:

• Molecular Biology
• Immunology
• Oncology

Background:

• MicroRNA-21 (miR-21) is an oncogene implicated in lung cancer development.
• The precise role of miR-21 in modulating the immune response within the tumor microenvironment requires further elucidation.

Purpose of the Study:

• To investigate the effect of miR-21 on immune response in lung tumorigenesis.
• To identify potential targets of miR-21 involved in immune modulation.

Main Methods:

• Compared mRNA expression of immune-related genes in wild-type and miR-21 knock-in mice using NanoString technology.
• Validated gene expression changes with real-time PCR and examined E-Selectin (Sele) protein levels via immunohistochemistry and Western blot.
• Analyzed the 3' untranslated region of mouse Sele for miR-21 binding sites and assessed Sele levels in transfected cells.

Main Results:

• Found significantly increased Sele mRNA and decreased Sele protein levels in miR-21 knock-in mice lungs.
• Confirmed that the 3' untranslated region of mouse Sele is targeted by miR-21.
• Observed decreased Sele levels in miR-21 mimic-transfected mouse lung bronchial epithelial cells.

Conclusions:

• E-Selectin (Sele) is a direct target of miR-21.
• The opposing changes in Sele mRNA and protein suggest a post-transcriptional feedback-regulation mechanism.
• Caution is advised when interpreting mRNA expression data from arrays, as they may not accurately reflect protein expression levels in miR-21-regulated pathways.