RESUMO
Approximately 31% of patients with 22q11.2 deletion syndrome (22q11.2DS) have genitourinary system disorders and 6% of them have undescended testes. Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS. In this study, we used mice with single-allele deletion in mitochondrial ribosomal protein L40 (Mrpl40 +/- ) as models to investigate the function of Mrpl40 in testes and spermatozoa development. The penetrance of cryptorchidism in Mrpl40 +/- mice was found to be higher than that in wild-type (WT) counterparts. Although the weight of testes was not significantly different between the WT and Mrpl40 +/- mice, the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40 +/- mice. Moreover, the concentration and motility of spermatozoa were significantly decreased in the Mrpl40 +/- mice. In addition, data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40 +/- testes. Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count. These findings suggest that Mrpl40 is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.
RESUMO
Type I interferons (IFN), which activate many IFN-stimulated genes (ISG), are known to regulate tumorigenesis. However, little is known regarding how various ISGs coordinate with one another in developing antitumor effects. Here, we report that the ISG UBA7 is a tumor suppressor in breast cancer. UBA7 encodes an enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of another ISG (ISG15) to cellular proteins in a process known as "ISGylation." ISGylation of other ISGs, including STAT1 and STAT2, synergistically facilitates production of chemokine-receptor ligands to attract cytotoxic T cells. These gene-activation events are further linked to clustering and nuclear relocalization of STAT1/2 within IFN-induced promyelocytic leukemia (PML) bodies. Importantly, this coordinated ISG-ISGylation network plays a central role in suppressing murine breast cancer growth and metastasis, which parallels improved survival in patients with breast cancer. These findings reveal a cooperative IFN-inducible gene network in orchestrating a tumor-suppressive microenvironment. SIGNIFICANCE: We report a highly cooperative ISG network, in which UBA7-mediated ISGylation facilitates clustering of transcription factors and activates an antitumor gene-expression program. These findings provide mechanistic insights into immune evasion in breast cancer associated with UBA7 loss, emphasizing the importance of a functional ISG-ISGylation network in tumor suppression.This article is highlighted in the In This Issue feature, p. 327.
Assuntos
Neoplasias da Mama/genética , Interferon Tipo I/genética , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT2/genética , Enzimas Ativadoras de Ubiquitina/genética , Animais , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/imunologia , Humanos , Camundongos , Linfócitos T/imunologia , Fatores de Transcrição/genética , Ubiquitinas/genética , Ubiquitinas/imunologiaRESUMO
This study uncovered microbial characteristics of bioelectricity generation and dye decolorization in single-chamber microbial fuel cells (MFCs) using activated sludge for wine-containing wastewater treatment. Phylogenetic tree analysis on 16S rRNA gene fragments indicated that the predominant strains on anodic biofilm in acclimatized MFCs were Gamma-Proteobacteria Aeromonas punctata NIU-P9, Pseudomonas plecoglossicida NIU-Y3, Pseudomonas koreensis NIU-X8, Acinetobacter junii NIU-Y8, Stenotrophomonas maltophila NIU-X2. Our findings showed that the current production capabilities of these pure strains were only ca. 10% of those of their mother activated sludge, indicating that synergistic interactions among microbes might be the most influential factor to maximize power generation in MFCs. Plus, these electrochemically active strains also performed reductive decolorization of C.I. reactive blue 160, suggesting that bioelectricity generation might be directly associated to azo dye decolorization to deal with electron transfer on anodic biofilm in MFCs.