ABSTRACT
Localized in the mitochondria, SIRT4 is a nicotinamide adenine dinucleotide (NAD +) -dependent adenosine diphosphate (ADP) -ribosyltransferase and is one of the least characterized members of the sirtuin family. Although it is well known that it shows deacetylase activity for energy metabolism, little is understood about its function in tumorigenesis. Recent research suggests that SIRT4 may work as both a tumor suppressor gene and an oncogene. However, the clinical significance of SIRT4 in prostate cancer remains unknown. In this study, we evaluated SIRT4 protein levels in cancerous prostate tissue and corresponding non-tumor prostate tissue via immunohistochemical staining on a tissue microarray including tissues from 89 prostate cancer patients. The association between SIRT4 expression and Gleason score was also determined. Further, shSIRT4 or stable prostate cancer cell lines (22RV1) overexpressing SIRT4 were constructed via lentiviral infection. Using Cell-Counting Kit-8 (CCK-8) assay, wound healing assay, migration, and invasion and apoptosis assays, the effects of SIRT4 on the migration, invasion ability, and proliferation of prostate cancer cells were investigated. We also determined the effect of SIRT4 on glutamine metabolism in 22RV1 cells. We found the protein levels of SIRT4 in prostate cancer tissues were significantly lower than those in their non-neoplastic tissue counterparts (P < 0.01); a lower SIRT4 level was also significantly associated with a higher Gleason score (P < 0.01). SIRT4 suppressed the migration, invasion capabilities, and proliferation of prostate cancer cells and induced cellular apoptosis. Furthermore, the invasion and migration of 22RV1 cells were mechanistically inhibited by SIRT4 via glutamine metabolism inhibition. In conclusion, the present study's findings showed that SIRT4 protein levels are significantly associated with the Gleason score in patients with prostate cancer, and SIRT4 exerts a tumor-suppressive effect on prostate cancer cells by inhibiting glutamine metabolism. Thus, SIRT4 may serve as a potential novel therapeutic target for prostate cancer.
Subject(s)
Prostatic Neoplasms , Sirtuins , Apoptosis , Cell Line, Tumor , Cell Proliferation , Genes, Tumor Suppressor , Glutamine/metabolism , Humans , Male , Mitochondrial Proteins/metabolism , NAD/metabolism , Prostatic Neoplasms/genetics , Sirtuins/genetics , Sirtuins/metabolismABSTRACT
BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disorder. Up to now, reports on the clinical characteristics of MPS IVA mainly focused on patients with progressive bone dysplasia and multiple organ damage, while the effects of this disorder on neurogenic bladder have not been reported. Therefore, the aim of the present study is to report two cases of nocturnal enuresis finally diagnosed as neurogenic bladder in MPS IVA. CASE PRESENTATION: Both children were characterized by the presence of pectus carinatum, kyphoscoliosis, nocturnal enuresis, urinary incontinence, normal intelligence, and loss of strength in the legs, diagnosed as neurogenic bladder in association with MPS IVA through the analysis of the clinical characteristics, enzyme activity and genetic testing. In addition, the terminator codon mutation c.1567T > G (p.X523E) and a novel missense mutation c.575A > G (p.E192G) were found in the coding region of the GALNS gene of the 1st patient, while the missense mutation c.488C > A (p.P163H) was found in the coding region of the GALNS gene of the 2nd patient. CONCLUSIONS: Neurogenic bladder may occur in patients with MPS IVA after spinal cord injury. It is necessary to screen for the diagnosis of MPS IVA in patients with atypical enuresis and skeletal abnormalities through the analysis of the clinical characteristics, enzyme activity and genetic testing.
