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

• Type of Material: Article
• Authors: Siyuan Tang, Emory University; Bailong Liu, Emory University; Jiaqi Liu, Emory University; Jian Wang, Emory University; Ya Wang, Emory University
• Language: English
• Date: 2019-05-01
• Publisher: TAYLOR & FRANCIS LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Rights managed by Taylor & Francis
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/09553002.2019.1564082
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
• Volume: 95
• Issue: 5
• Start Page: 580
• End Page: 584
• Grant/Funding Information: This work is supported by grants from the National Aeronautics and Space Administration (NNX11AC30G to Y.W.) and the National Cancer Institute (CA186129, CA185882 to Y.W. and P30CA138292 to the Institute).
• Keywords: miR-21; Science & Technology; Biology; immune response; Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine & Medical Imaging; CANCER; radiation; LUNG TUMORIGENESIS; Sele; lung tumorigenesis; Nuclear Science & Technology; Technology; Life Sciences & Biomedicine

Abstract

Purpose: To study whether miR-21, an oncogene associated with lung tumorigenesis, affects immune response. Material and methods: Cancer immune-related 786 mRNA expression was compared in lung tissue from wild-type and miR-21 knock-in mice using NanoString technology. The significantly changed genes were verified using real-time PCR. E-Selectin (Sele) was subsequently identified for further examination using immunohistochemistry (IHC) and Western blot in the same lung tissue. The mouse Sele 3’untranslated region (3’-UTR) was searched to identify a miR-21 matching sequence. The Sele level in miR-21 mimic transfected mouse lung bronchial epithelial (LBE) cells was examined. Results: We unexpectedly found that the Sele mRNA level significantly increased but the protein level significantly decreased in the lung tissue of miR-21 knock-in mice compared to the mRNA/protein levels in the lung tissue of wild-type mice. The mouse Sele 3'-UTR contains the key sequence that can be targeted by miR-21. The Sele levels decreased in mouse LBE cells after miR-21 mimic transfection. Conclusion: Sele is a potential miR-21 target. The opposing Sele levels at mRNA and protein suggest a feedback-regulation from protein to mRNA. The feedback-regulation in miR-21-suppressed gene expression indicates that we should carefully evaluate any data from mRNA array since they may not reflect real protein expression status.