Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry

• DOI: 10.1016/j.tranon.2023.101680
• Publication Date: 2023-04-28T22:42:13Z
• Authors: Estefania Contrer...; Ángeles Carlos-Reyes; Mónica Sierra-Mar...; Gustavo Acosta-Al...; Cesar Luna-Rivero; David Núñez-Corona; Alejandra Paola G...; Eloisa Ibarra-Sierra; Horacio Vidrio-Mo...; María Elizbeth Al...; Laurence A. Marchat; César López-Camar...
• Keywords: Vasculogenic mimicry; CD31; Hypoxia

Tumor cells grow in three-dimensional (3D) channels-like structures denoted as vasculogenic mimicry (VM), which provides a route for nutrients and oxygen acquisition. VM is activated by hypoxia associated with metastasis poor prognosis. MetastamiRs are microRNAs regulating metastasis, however, if they control breast cancer remains poorly understood. The aim of this study was to evaluate the expression VM-associated tumors metastatic patients. Firstly, we constructed microRNAs/mRNAs coregulation networks using data from TCGA databases. Dozens genes involved were found. Of these, selected 10 further characterization. presence histological samples patients or without evaluated CD31-/PAS+ immunophenotyping. Remarkably, showed that significantly increased comparison no-metastatic group. Gene analysis indicated miR-145, miR-142-3p, miR-31, miR-148a, miR-200b-3p miR-526b downregulated primary disease positive VM. Moreover, modulated predictive clinical value overall survival cohort (n=1262) role miR-145 formation hypoxia-induced 3D an vitro model recapitulates early stages Data mimics able abolish development both Hs578t MDA-MB-231 cells. In conclusion, manipulation levels may represent therapeutic approach developed