Background. Invasive breast carcinoma (BRCA) is a common type of breast cancer with a high clinical incidence. Thus, it is significant to find effective biomarkers for BRCA diagnosis and treatment. Although some members of armadillo (ARM) repeat family of proteins are confirmed to be biomarkers in cancers, the role of armadillo repeat-containing 1 (ARMC1) in BRCA remains unknown. Methods. We firstly analyzed the ARMC1 expression in normal breast tissues and BRCA samples and its association with overall survival by the public database. Next, the χ 2 test was used to evaluate the prognostic significance of ARMC1 expression in TCGA-BRCA patient samples. The ARMC1 mutations in BRCA were explored in the cBioportal database. Besides, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the biological functions of ARMC1 in BRCA. Finally, immunohistochemistry and immunofluorescence staining were performed to validate the ARMC1 expression in BRCA. Results. ARMC1 expression in tumor samples was significantly higher than that in normal tissues, and higher expression of ARMC1 was related to lower survival. Moreover, the tumor stage and histology of BRCA patients were associated with ARMC1 expression. ARMC1 genetic mutations occurred in 32% of BRCA patients, and the amplification and high expression of ARMC1 accounted for most of them. Furthermore, functional enrichment analysis suggested that ARMC1 might be involved in the cell cycle in BRCA. Ultimately, increased ARMC1 expression was found in clinical breast carcinoma tissues by our confirmatory experiments. Conclusions. ARMC1 may play a significant role in BRCA and act as a biomarker, which provides valuable clues for the treatment and diagnosis of BRCA.
BackgroundEpilepsy is a common neurological disease, and excessive mitophagy is considered as one of the major triggers of epilepsy. Mitophagy is a crucial pathway affecting reactive oxygen species. Phosphoglycerate mutase 5 (PGAM5) is a protein phosphatase present in mitochondria that regulates many biological processes including mitophagy and cell death. However, the mechanism of PGAM5 in epilepsy remains unclear. The purpose of the present study was to examine whether PGAM5 affects epilepsy through PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy.MethodsAfter the knockdown of PGAM5 expression by the adeno-associated virus, an epilepsy model was created by kainic acid. Next, the seizure activity was recorded by local field potentials before evaluating the level of mitochondrial autophagy marker proteins. Lastly, the ultrastructure of mitochondria, neuronal damage and oxidative stress levels were further observed.ResultsA higher PGAM5 level was found in epilepsy, and its cellular localization was in neurons. The interactions between PGAM5 and PINK1 in epilepsy were further found. After the knockdown of PGAM5, the level of PINK1 and light chain 3B was decreased and the expression of the translocase of the inner mitochondrial membrane 23 and translocase of the outer mitochondrial membrane 20 were both increased. Knockdown of PGAM5 also resulted in reduced neuronal damage, decreased malondialdehyde levels, decreased reactive oxygen species production and increased superoxide dismutase activity. In addition, the duration of spontaneous seizure-like events (SLEs), the number of SLEs and the time spent in SLEs were all reduced in the epilepsy model after inhibition of PGAM5 expression.ConclusionInhibition of PGAM5 expression reduces seizures via inhibiting PINK1-mediated mitophagy.
Background: Invasive breast carcinoma (BRCA) is a common type of breast cancer with high incidence in clinics, so it is significant to find an effective biomarker for BRCA diagnosis and treatment. Although some Armadillo (Arm)-repeat proteins families are confirmed to be biomarkers in cancers, the role of Armadillo repeat-containing 1 (ARMC1) in BRCA remains unknown.Methods: We analyzed the ARMC1 expression in normal breast tissues and BRCA samples, and its association with overall survival by the public database. χ² test evaluated the risks associated with ARMC1 expression in TCGA-BRCA patient samples. The ARMC1 mutations in BRCA were explored in the cBioportal database. Besides, the GO and KEGG analysis was used to explore the potential signaling pathways of ARMC1 in BRCA. Lastly, Immunohistochemistry and immunohistochemistry were performed to validate the ARMC1 expression in BRCA.Results: ARMC1 level in tumor sample was significantly higher than that in normal tissue, and it was also related to lower survival. The factors in clinical patients such as tumor stage and grade and histology were associated with ARMC1 expression. There were 32% of ARMC1 genetic mutations in BRCA, and the amplification and high expression made up the majority of them. Also, ARMC1 might regulate BRCA by involving in the cell cycle. Increased ARMC1 expression was found in clinical breast carcinoma tissues by our confirmatory experiments.Conclusions: All the results revealed that ARMC1 may play a significant role in BRCA as a biomarker, it provides valuable clues for the treatment and diagnosis of invasive breast cancer.
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