Document Type
Article
Publication Date
5-16-2023
Abstract
Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% decrease in ESCC incidence vs. Zn-untreated controls. Zn treatment eliminated ESCCs by affecting a spectrum of biological processes that included downregulation of expression of the two miRs and miR-31-controlled inflammatory pathway, stimulation of miR-21-PDCD4 axis apoptosis, and reversal of the ESCC metabolome: with decrease in putrescine, increase in glucose, accompanied by downregulation of metabolite enzymes ODC and HK2. Thus, Zn treatment or miR-31/21 silencing are effective therapeutic strategies for ESCC in this rodent model and should be examined in the human counterpart exhibiting the same biological processes.
Recommended Citation
Fong, Louise; Huebner, Kay; Jing, Ruiyan; Smalley, Karl; Brydges, Christopher R; Fiehn, Oliver; Farber, John; and Croce, Carlo M, "Zinc Treatment Reverses and anti-Zn-Regulated miRs Suppress Esophageal Carcinomas In Vivo" (2023). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 396.
https://jdc.jefferson.edu/pacbfp/396
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
37155893
Language
English
Included in
Cancer Biology Commons, Cell Anatomy Commons, Cell Biology Commons, Genetics Commons, Medical Pathology Commons, Neoplasms Commons
Comments
This article is the author's final published version in Proceedings of the National Academy of Sciences of the United States of America, Volume 120, Issue 20, 2023, Article number e2220334120.
The published version is available at https://doi.org/10.1073/pnas.2220334120.
Copyright © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).