RESUMO
Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.
Assuntos
Regulação Neoplásica da Expressão Gênica , Metaloproteinase 9 da Matriz , MicroRNAs , Metástase Neoplásica , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Feminino , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Linhagem Celular Tumoral , Animais , Camundongos , Camundongos Nus , Movimento Celular/genética , Camundongos Endogâmicos BALB CRESUMO
IMPORTANCE: Candida albicans is a major human fungal pathogen, and antimicrobial peptides are key components of innate immunity. Studying the interplay between C. albicans and human antimicrobial peptides would enhance a better understanding of pathogen-host interactions. Moreover, potential applications of antimicrobial peptides in antifungal therapy have aroused great interest. This work explores new mechanisms of LL-37 against C. albicans and reveals the complex connection among calcium homeostasis, oxidative stress, signaling, and possibly organelle interaction. Notably, these findings support the possible use of antimicrobial peptides to prevent and treat fungal infections.
Assuntos
Candida albicans , Catelicidinas , Humanos , Candida albicans/metabolismo , Catelicidinas/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Cálcio , Peptídeos Antimicrobianos , Membrana Celular/metabolismo , Homeostase , Antifúngicos/farmacologia , Antifúngicos/uso terapêuticoRESUMO
Breast cancer is a leading cause of cancer-related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (DPDS) in breast cancer cell lines. DPDS inhibited cellular proliferation and viability in a dose-dependent manner and reduced colony formation, an index of clonogenicity. Annexin-V and 7-AAD double staining showed that DPDS could induce the apoptosis of breast cancer cells. Western blotting of the expression of Bax p21 and its cleaved form p18 suggested the activation of p18 Bax-induced apoptosis. Furthermore, the increased expression of the autophagy marker LC3B-II indicated autophagic lysosome accumulation induced by DPDS. Our findings suggest that DPDS has potential as a candidate for treating breast cancer, and further modifications and optimizations are warranted.