{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":52,"searchCount":0},"additional":{"submitter":["Tse J"],"funding":["Austin Medical Research Foundation","Government of Victoria","National Health and Medical Research Council"],"pagination":["264"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8773769"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(2)"],"pubmed_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."],"journal":["Cancers"],"pubmed_title":["Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression."],"pmcid":["PMC8773769"],"funding_grant_id":["1173814","Project grant","1079257","1092788","Operational Infrastructure Support Program"],"pubmed_authors":["Marcusson EG","Tse J","Ernst M","Pierce T","Thiem S","Alorro MG","Carli ALE","Buchert M"],"view_count":["52"],"additional_accession":[]},"is_claimable":false,"name":"Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression.","description":"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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2024-11-08T11:16:44.649Z","creation":"2022-02-11T16:00:43.033Z"},"accession":"S-EPMC8773769","cross_references":{"pubmed":["35053428"],"doi":["10.3390/cancers14020264"]}}