Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/28642
Title: | Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression. | Austin Authors: | Tse, Janson;Pierce, Thomas;Carli, Annalisa L E;Alorro, Mariah G;Thiem, Stefan;Marcusson, Eric G;Ernst, Matthias ;Buchert, Michael | Affiliation: | Olivia Newton-John Cancer Research Institute School of Cancer Medicine, La Trobe University, Melbourne 3083, Australia Regulus Therapeutics, 10628 Science Center Drive, San Diego, CA 92121, USA Marcusson Consulting, 239 Brannan Street, San Francisco, CA 94107, USA |
Issue Date: | 6-Jan-2022 | Date: | 2022 | Publication information: | Cancers 2022; 14(2): 264 | Abstract: | MicroRNA-21 (miR-21) is a small, non-coding RNA overexpressed in gastric cancer and many other solid malignancies, where it exhibits both pro-and anti-tumourigenic properties. However, the pathways regulating miR-21 and the consequences of its inhibition in gastric cancer remain incompletely understood. By exploiting the spontaneous Stat3-dependent formation of inflammation-associated gastric tumors in Gp130F/F mice, we functionally established miR-21 as a Stat3-controlled driver of tumor growth and progression. We reconciled our discoveries by identifying several conserved Stat3 binding motifs upstream of the miR-21 gene promoter, and showed that the systemic administration of a miR-21-specific antisense oligonucleotide antagomir reduced the established gastric tumor burden in Gp130F/F mice. We molecularly delineated the therapeutic benefits of miR-21 inhibition with the functional restoration of PTEN in vitro and in vivo, alongside an attenuated epithelial-to-mesenchymal transition and the extracellular matrix remodeling phenotype of tumors. We corroborated our preclinical findings by correlating high STAT3 and miR-21 expression with the reduced survival probability of gastric cancer patients. Collectively, our results provide a molecular framework by which miR-21 mediates inflammation-associated gastric cancer progression, and establish miR-21 as a robust therapeutic target for solid malignancies characterized by excessive Stat3 activity. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/28642 | DOI: | 10.3390/cancers14020264 | ORCID: | 0000-0003-2672-0148 0000-0002-6399-1177 |
Journal: | Cancers | PubMed URL: | 35053428 | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/35053428/ | ISSN: | 2072-6694 | Type: | Journal Article | Subjects: | EMT Stat3 TME antagomir miR-21 stomach tumor |
Appears in Collections: | Journal articles |
Show full item record
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.