CD97 shows a strong relationship with metastasis and poor clinical outcome in various tumors, including ovarian cancer. The expression of CD97 in metastatic ovarian cancer cells was higher than that in primary ovarian cancer cells. Mature miRNAs are frequently de-regulated in cancer and incorporated into a specific mRNA, leading to post-transcriptional silencing. In this study, we investigated whether the miR-503-5p targeting of the CD97 3'-untranslated region (3'-UTR) contributes to ovarian cancer metastasis as well as the underlying mechanism regulating cancer progression. In LPS-stimulated or paclitaxel-resistant ovarian cancer cells, stimulation with recombinant human CD55 (rhCD55) of CD97 in ovarian cancer cells activated NF-κB-dependent miR-503-5p down-regulation and the JAK2/STAT3 pathway, consequently promoting the migratory and invasive capacity. Furthermore, restoration of miR-503-5p by transfection with mimics or NF-κB inhibitor efficiently blocked CD97 expression and the downstream JAK2/STAT3 signaling pathway. Target inhibition of JAK with siRNA also impaired colony formation and metastasis of LPS-stimulated and paclitaxel-resistant ovarian cancer cells. Taken together, these results suggest that high CD97 expression, which is controlled through the NF-κB/miR-503-5p signaling pathway, plays an important role in the invasive activity of metastatic and drug-resistant ovarian cancer cells by activating the JAK2/STAT3 pathway.

Spandidos Publications is a scientific publisher with a long-standing international reputation for excellent standards and high quality science publications

In cancer, resistance to chemotherapy is one of the main reasons for therapeutic failure. Cells that survive after treatment with anticancer drugs undergo various changes, including in cell metabolism. In this study, we investigated the effects of AKT-mediated miR-125b-5p alteration on metabolic changes and examined how these molecules enhance migration and induce drug resistance in colon cancer cells. AKT1 and AKT3 activation in drug-resistant colon cancer cells caused aberrant downregulation of miR-125b-5p, leading to GLUT5 expression. Targeted inhibition of AKT1 and AKT3 restored miR-125b-5p expression and prevented glycolysis- and lipogenesis-related enzyme activation. In addition, restoring the level of miR-125b-5p by transfection with the mimic sequence not only significantly blocked the production of lactate and intracellular fatty acids but also suppressed the migration and invasion of chemoresistant colon cancer cells. GLUT5 silencing with small interfering RNA attenuated mesenchymal marker expression and migratory activity in drug-resistant colon cancer cells. Additionally, treatment with 2,5-anhydro-d-mannitol resensitized chemoresistant cancer cells to oxaliplatin and 5-fluorouracil. In conclusion, our findings suggest that changes in miR-125b-5p and GLUT5 expression after chemotherapy can serve as a new marker to indicate metabolic change-induced migration and drug resistance development.

Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a “multiplexed target” that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASC^miR-210) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASC^miR-210). Under hypoxic conditions, we observed that ASC^miR-210 inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASC^miR-210 did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASC^miR-210. These results suggest that the multiplexed target with ASC^miR-210 is a useful tool for cardiovascular regeneration.