Hypoxic Melanoma Cells Deliver microRNAs to Dendritic Cells and Cytotoxic T Lymphocytes through Connexin-43 Channels.

Alterations in microRNA (miRNA) profiles, induced by tumor microenvironment stressors, like hypoxia, allow cancer cells to acquire immune-resistance phenotypes. Indeed, hypoxia-induced miRNAs have been implicated in cancer progression through numerous cancer cell non-autonomous mechanisms, including the direct transfer of hypoxia-responsive miRNA from cancer to immune cells via extracellular vesicles. Connexin-43 (Cx43)-constituted gap junctions (GJs) have also been involved in miRNA intercellular mobilization, in other biological processes. In this report, we aimed to evaluate the involvement of Cx43-GJs in the shift of miRNAs induced by hypoxia, from hypoxic melanoma cells to dendritic cells and melanoma-specific cytotoxic T lymphocytes (CTLs). Using qRT-PCR arrays, we identified that miR-192-5p was strongly induced in hypoxic melanoma cells. Immune cells acquired this miRNA after co-culture with hypoxic melanoma cells. The transfer of miR-192-5p was inhibited when hypoxic melanoma cells expressed a dominant negative Cx43 mutant or when Cx43 expression was silenced using specific short-hairpin RNAs. Interestingly, miR-192-5p levels on CTLs after co-culture with hypoxic melanoma cells were inversely correlated with the cytotoxic activity of T cells and with ZEB2 mRNA expression, a validated immune-related target of miR-192-5p, which is also observed in vivo. Altogether, our data suggest that hypoxic melanoma cells may suppress CTLs cytotoxic activity by transferring hypoxia-induced miR-192-5p through a Cx43-GJs driven mechanism, constituting a resistance strategy for immunological tumor escape.

La continuidad de la formación en tiempos de pandemia y los aprendizajes de este proceso / Continuity of training in times of pandemic and learning from this process

En el contexto mundial desde diciembre del año 2019, a causa de la pandemia por COVID-19, han cobrado especial importancia las tecnologías de la información y comunicación (TIC) en todos los ámbitos, la formación de las nuevas generaciones en el área de la salud no es la excepción. La revolución digital y tecnológica en educación nos llevó a adelantarnos por lo menos 5 a 8 años en Chile y tal vez a nivel mundial. Esto evidencia la importancia de que los docentes universitarios deben desarrollar las competencias digitales necesarias para trabajar en el entorno actual.1,2 Tras la integración en las universidades de la educación digital en forma acelerada, debido a la pandemia a nivel mundial, se han tenido que reformar las estructuras universitarias y los procesos de enseñanza-aprendizaje y el uso de nuevas metodologías docentes. En estas reformas, tienen una función importante las TIC como recurso didáctico, objeto de estudio...(AU)