MicroRNA-27a Suppresses the Toxic Action of Mepivacaine on Breast Cancer Cells via Inositol-Requiring Enzyme 1-TNF Receptor-Associated Factor 2.

Objective: To investigate the toxic effects of microRNA-27a on breast cancer cells through inositol-acquiring enzyme 1-TNF receptor-associated factor 2 inhibition by mepivacaine. Methods: The elevation of miR-27a in MCF-7 of BCC lines was measured, and groups were set up as control, mepivacaine, and elevated groups. Cells from each group were examined for inflammatory progression. Results: Elevated miR-27a in MCF-7 cells was able to distinctly augment the cell advancement (P < 0.01) and decline cell progression (P < 0.01). Meanwhile, miR-27a reduced the content of intracellular inflammatory factors IL-1ß (P < 0.01) and IL-6 (P < 0.01), elevated the content of IL-10 (P < 0.01), suppressed levels of cleaved-caspase-3 and p-signal transducer and activator of transcription-3 (STAT3) (P < 0.01), and increased Bcl-2/Bax (P < 0.01). Conclusion: Elevated miR-27a in MCF-7 of BCC lineage was effective in reducing the toxic effects of mepivacaine on cells and enhancing cell progression. This mechanism is thought to be related to the activation of the IRE1-TRAF2 signaling pathway in BCC. The findings may provide a theoretical basis for targeted treatment of BC in clinical practice.

Delivery of miR-130a-3p Through Adipose-Derived Stem Cell-Secreted EVs Protects Against Diabetic Peripheral Neuropathy via DNMT1/NRF2/HIF1α/ACTA1 Axis.

Peripheral neuropathy is common in diabetic patients and can lead to amputations or foot ulcers. microRNAs (miRNAs) possess crucial roles in diabetic peripheral neuropathy (DPN). This study aims to investigate the role miR-130a-3p played in DPN and its underlying molecular mechanisms. miR-130a-3p expression in clinical tissue samples, established DPN rat models, and extracellular vesicles (EVs) derived from adipose-derived stem cells (ADSCs) were determined. Schwann cells (SCs) were co-cultured with ADSC-derived EVs and treated with high glucose. The direct relationship and functional significance of miR-130a-3p, DNMT1, nuclear factor E2-related factor 2 (NRF2), hypoxia-inducible factor-1α (HIF1α), and skeletal muscle actin alpha 1 (ACTA1) was identified. The in vitro and in vivo implication of ADSC-derived EVs carrying miR-130a-3p was assessed. miR-130a-3p was poorly expressed in DPN patients and rats but highly expressed in ADSC-derived EVs. miR-130a-3p could be delivered to SCs through ADSC-derived EVs to inhibit SC apoptosis and promote proliferation under a high-glucose environment. miR-130a-3p activated NRF2/HIF1α/ACTA1 axis through down-regulating DNMT1. In vivo injection of ADSC-derived EVs activated NRF2/HIF1α/ACTA11 axis to promote angiogenesis in DPN rat model. These data together supported that ADSC-derived EVs carrying miR-130a-3p could alleviate DPN by accelerating SC proliferation and inhibiting apoptosis, providing a potential treatment against DPN.