Infected wounds caused by persistent inflammation exhibit poor vascularization and cellular infiltration. In order to rapidly control the inflammatory effect and accelerate wound healing, it is necessary to develop a novel drug vehicle addressing the need for infected wounds. Herein, we developed a novel dual-drug delivery system with micrometer-scale alginate fibers encapsulated in instant self-assembly peptide hydrogel. Short peptides with the sequence of Nap-Gly-Phe-Phe-Lys-His (Nap-GFFKH) could self-assemble outside the microfluidic-based alginate microfibers in weak acidic solution (pH ≈ 6.0) within 5 s. The gelation condition is close to the pH environment of the human skin. We further constructed recombinant bovine basic fibroblast growth factor (FGF-2) in fibrous alginate, which was encapsulated in antibiotic-loaded peptide hydrogel. The dual-drug delivery system exhibited good mechanical property and sustained release profiles, where antibiotic could be rapidly released from the peptide hydrogel, while the growth factor could be gradually released within 7 days. Both in vitro antibacterial experiments and in vivo animal experiments confirmed that such a dual-drug delivery system has good antibacterial activity and enhances wound healing property. We suggested that the dual-drug delivery system could be potentially applied for controlled drug release in infected wound healing, drug combination for melanoma therapy, and tissue engineering.

Breast cancer, the most prevalent cancer type among women worldwide, remains incurable once metastatic. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in breast cancer by regulating specific genes or proteins. In this study, we found miR-133b was silenced in breast cancer cell lines and in breast cancer tissues, which predicted poor prognosis in breast cancer patients. We also confirmed that lncRNA NEAT1 was up-regulated in breast cancer and inhibited the expression of miR-133b, and identified the mitochondrial protein translocase of inner mitochondrial membrane 17 homolog A (TIMM17A) that serves as the target of miR-133b. Both miR-133b knockdown and TIMM17A overexpression in breast cancer cells promoted cell migration and invasion both in vitro and in vivo. In summary, our findings reveal that miR-133b plays a critical role in breast cancer cell metastasis by targeting TIMM17A. These findings may provide new insights into novel molecular therapeutic targets for breast cancer.

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Breast cancer is the most prevalent cancer in women worldwide, which remains incurable once metastatic. Breast cancer stem cells (BCSCs) are a small subset of breast cancer cells, which are the radical cause of drug resistance, tumor relapse, and metastasis in breast cancer. The extracellular serine protease inhibitor serpinE2, also named protease nexin-1 (PN-1), contributes to enhanced metastasis of cancer cells mainly by remodeling the tumor matrix. In this study, we found that PN-1 was up-regulated in breast cancer, which promoted cell invasion, migration and stemness. Furthermore, by using specific inhibitors, we discovered that epidermal growth factor (EGF) up-regulated PN-1 in breast cancer cells through cascade activation of epidermal growth factor receptor (EGFR) to the activation of protein kinase Cδ (PKCδ), mitogen-activated protein kinase (MEK) and extracellular signal-related kinase (ERK), which finally led to the up-regulation of early growth response protein 1 (EGR1). Moreover, EGF signaling was further activated as a feedback of PN-1 up-regulation through PN-1 blocking HtrA1. Taken together, our findings revealed a novel signaling axis that up-regulated PN-1 expression in breast cancer cells, and the new mechanism of PN-1-promoted breast cancer metastasis, which may provide new insights into identifying novel therapeutic targets for breast cancer.

BackgroundmiR-133a-3p has been recently discovered to be down-regulated in various human malignancies, including breast cancer, and reduced miR-133a-3p levels have been significantly associated with breast cancer cell growth and invasion. However, the regulatory mechanisms leading to abnormal expression of miR-133a-3p in breast cancer remain obscure.MethodsqRT-PCR was applied to detect the expression of miR-133a-3p in breast cancer tissues and cell lines. Bisulfite sequencing was used to detect the degree of methylation of the miR-133a-3p promoter. The effects of miR-133a-3p on breast cancer in vitro were examined by cell proliferation assay, transwell assay, flow cytometry, and western blotting. Bioinformatic analysis, dual-luciferase assay and RIP assay were employed to identify the interaction between miR-133a-3p and MAML1. A xenograft model was used to show the metastasis of breast cancer cells.ResultsWe confirmed that miR-133a-3p was silenced by DNA hypermethylation in breast cancer cell lines and tissues, which predicted poor prognosis in breast cancer patients, and reducing miR-133a-3p expression led to a significant increase in the migration, invasion, proliferation, and stemness of breast cancer cells in vitro. Mastermind-like transcriptional coactivator 1 (MAML1) was confirmed to be a target of miR-133a-3p involved in regulating breast cancer metastasis both in vitro and in vivo. Moreover, a series of investigations indicated that MAML1 initiated a positive feedback loop, which could up-regulate DNA methyltransferase 3A (DNMT3A) to promote hypermethylation of the miR-133a-3p promoter.ConclusionTaken together, our findings revealed a novel miR-133a-3p/MAML1/DNMT3A positive feedback loop in breast cancer cells, which may become a potential therapeutic target for breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1400-z) contains supplementary material, which is available to authorized users.