Female ; Humans ; Sarcoma, Endometrial Stromal/surgery* ; Transcription Factors/genetics* ; Endometrial Neoplasms/surgery* ; DNA-Binding Proteins ; Co-Repressor Proteins ; Repressor Proteins/genetics*

Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.
Humans ; Carcinoma, Renal Cell/genetics* ; Fructose-Bisphosphate Aldolase/metabolism* ; Co-Repressor Proteins/metabolism* ; Transcription Factors/genetics* ; Kidney Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic

Humans ; Neoplasms/genetics* ; Nuclear Proteins ; Co-Repressor Proteins ; Cell Line, Tumor ; Molecular Chaperones

FAM60A,a cell cycle protein,is a subunit of the SIN3 transcription regulator family member A/histone deacetylase(SIN3-HDAC)complex and plays an important role in cell cycle regulation,cell morphology change,cell proliferation,differentiation and migration,early embryogenesis and so on.Studies in recent years have shown that FAM60A plays a role in the occurrence and development of tumors including human osteosarcoma,esophageal cancer,gastric cancer,lung cancer and liver cancer,providing a new research direction for tumor diagnosis and treatment.Based on the research results in recent years at home and abroad,this paper discussed the effects of FAM60A on cellular functions.
Cell Cycle Proteins ; Cell Differentiation ; Cell Proliferation ; DNA-Binding Proteins ; Humans ; Sin3 Histone Deacetylase and Corepressor Complex

OBJECTIVE: To summarize clinical manifestations, inheritance pattern and mutations of NR0B1 gene in 7 children with X-linked adrenal dysplasia congenita (XL-AHC). METHODS: Clinical data of the 7 children was collected. Next-generation sequencing was carried out to detect potential mutations in the coding regions of adrenal gland-related genes. Suspected mutations were verified with Sanger sequencing. RESULTS: In all of the children, the initial symptom was adrenocortical insufficiency. Five cases had neonatal onset, while the remaining two developed it at the age of 2. Three cases (42.9%) had a short stature and 1 showed growth retardation (14.3%). Of the 7 cases, 6 (85.7%) had mutations occurring in exon 1, and 1 (14.3%) had it occurring in exon 2. Four cases (57.1%) were frameshift mutations, 2 cases (28.6%) were nonsense mutations and 1 case (14.3%) was missense mutation. Two mutations were known to be pathogenic, and 5 had not been reported previously. Maternal inheritance was found in 6 cases. Three children had a maternal uncle died of unexplained causes. The mothers of 2 children had a history of spontaneous abortions. One child had a brother died of unexplained reason. CONCLUSION Male children with primary adrenal insufficiency should be routinely checked for NR0B1 mutations, especially those with a family history. mutations of NR0B1 gene occur mostly in exon 1, with frameshift mutations being the most common type. The development of all patients with XL-AHC should be closely monitored during follow-up.
Adrenal Insufficiency ; Child ; DAX-1 Orphan Nuclear Receptor ; DNA Mutational Analysis ; Genes, X-Linked ; Humans ; Hypoadrenocorticism, Familial ; Male ; Mutation

OBJECTIVE: To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations. METHODS: Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production. RESULTS: Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous. CONCLUSION The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
Adrenal Insufficiency ; DAX-1 Orphan Nuclear Receptor ; genetics ; Humans ; Hypoadrenocorticism, Familial ; genetics ; Male ; Mutation ; Mutation, Missense ; Pedigree ; Repressor Proteins

The study is aimed to construct high quality Salvia miltiorrhiza cDNA library and obtain the SmJAZ8 gene of S. miltiorrhiza by yeast two-hybrid system. In this study， full-length cDNA was synthesized from roots， stems， leaves， flowers and hairy roots of S. miltiorrhiza. The full-length cDNA library was synthesized by SMART method and constructed with DSN homogenization technique. The results showed that the library capacity was 1.45×10⁶， the recombination rate was 100%， and the average size of the insert was 500-2 000 bp. The recombinant vector of pDEST-pGADT7-SmJAZ8 was constructed and transformed into Y2HGold strain. The interaction protein was screened by yeast two-hybrid system. The DnaJ protein and UBQ protein were screened by yeast two-hybrid system. This study has successfully constructed a full-length cDNA library of S. miltiorrhiza， and laid the foundation for the follow-up study on functional gene screening and gene function of S. miltiorrhiza.
Co-Repressor Proteins ; genetics ; DNA, Complementary ; Gene Library ; Plant Proteins ; genetics ; Salvia miltiorrhiza ; genetics ; Two-Hybrid System Techniques

OBJECTIVE: To explore the pathogenesis of a 46,XY female with sex reversal. METHODS: Peripheral blood lymphocytes of the patient were subjected to G-banding karyotype analysis. Sex chromosomes were analyzed with fluorescence in situ hybridization (FISH). SRY gene was analyzed by Sanger sequencing. The whole exome of the patient was subjected to next generation sequencing. Copy number variations (CNVs) of the NR0B1, SF1, SRY, SOX9 and WNT4 genes were validated by multiplex ligation-dependent probe amplification (MLPA). RESULTS: The patient had a 46,XY karyotype. FISH analysis showed that her sex chromosomes were X and Y. No mutation was found in the SRY gene, and no pathogenic mutation was detected in her exome. However, a duplication spanning approximately 67.31 kb encompassing the MAGEB1, MAGEB3, MAGEB4 and NR0B1 genes at Xp21, was predicted by software analysis. MLPA confirmed duplication of the NR0B1 gene in the patient and her mother. CONCLUSION A duplication fragment of Xp21 encompassing the NR0B1 gene in the 46,XY female with sex reversal is transmitted from her asymptomatic carrier mother. Attention should be paid towards the insidious nature and high morbidity of this duplication.
DAX-1 Orphan Nuclear Receptor ; genetics ; DNA Copy Number Variations ; Female ; Gene Duplication ; Genes, sry ; Gonadal Dysgenesis, 46,XY ; genetics ; Humans ; In Situ Hybridization, Fluorescence

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein involved in both genomic and nongenomic estrogen signal transduction pathways. To date, the role of PELP1 protein has yet to be characterized in human sperm and has not been associated with sperm parameters. To confirm the presence of PELP1 in human sperm, fresh semen samples were obtained from 178 donors. The study was designed to establish both mRNA and protein presence, and protein cellular localization. Additionally, the number of PELP1-positive spermatozoa was analyzed in men with normal and abnormal semen parameters. Sperm parameters were assessed according to the World Health Organization (WHO) 2010 standards. The presence of PELP1 in spermatozoa was investigated using four precise, independent techniques. The qualitative presence of transcripts and protein was assessed using reverse transcription-polymerase chain reaction (RT-PCR) and western blot protocols, respectively. The cellular localization of PELP1 was investigated by immunocytochemistry. Quantitative analysis of PELP1-positive cells was done by flow cytometry. PELP1 mRNA and protein was confirmed in spermatozoa. Immunocytochemical analysis identified the presence of PELP1 in the midpieces of human sperm irrespective of sperm parameters. Becton Dickinson fluorescence-activated cell sorting (FACSCalibur™) analysis revealed a significantly lower number of PELP1-positive cells in males with normal semen parameters versus abnormal samples (42.78% ± 11.77% vs 61.05% ± 21.70%, respectively; P = 0.014). The assessment of PELP1 may be a time-saving method used to obtain information about sperm quality. The results of our study suggest that PEPL1 may be utilized as an indicator of sperm quality; thereby, PELP1 may be an additional biomarker useful in the evaluation of male infertility.
Adolescent ; Adult ; Biomarkers/metabolism* ; Co-Repressor Proteins/metabolism* ; Humans ; Infertility, Male/metabolism* ; Male ; Middle Aged ; Semen Analysis ; Sperm Motility/physiology* ; Spermatozoa/metabolism* ; Transcription Factors/metabolism* ; Young Adult

PURPOSE: Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS: Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS: TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. CONCLUSION: High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.
Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Co-Repressor Proteins ; Disease-Free Survival ; Estrogens ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Triple Negative Breast Neoplasms