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

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