[Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy].

Temozolomide resistance is a major cause of recurrence and poor prognosis in neuroglioma. Recently, growing evidence has suggested that mitophagy is involved in drug resistance in various tumor types. However, the role and molecular mechanisms of mitophagy in temozolomide resistance in glioma remain unclear. In this study, mitophagy levels in temozolomide-resistant and -sensitive cell lines were evaluated. The mechanisms underlying the regulation of mitophagy were explored through RNA sequencing, and the roles of differentially expressed genes in mitophagy and temozolomide resistance were investigated. We found that mitophagy promotes temozolomide resistance in glioma. Specifically, small ubiquitin-like modifier specific protease 6 (SENP6) promoted temozolomide resistance in glioma by inducing mitophagy. Protein-protein interactions between SENP6 and the mitophagy executive protein PTEN-induced kinase 1 (PINK1) resulted in a reduction in small ubiquitin-like modifier 2 (SUMO2)ylation of PINK1, thereby enhancing mitophagy. Our study demonstrates that by inducing mitophagy, the interaction of SENP6 with PINK1 promotes temozolomide resistance in glioblastoma. Therefore, targeting SENP6 or directly regulating mitophagy could be a potential and novel therapeutic target for reversing temozolomide resistance in glioma.

Regenerating gene IA predicts radiosensitivity and survival in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. Radiotherapy is the main treatment option. However, radiotherapy does not benefit all patients because there is no known precise biomarker that can be used for screening radioresistant patients. Genetic predisposition is closely related to tumor development, therapeutic response, and prognosis. The relationship between regenerating gene IA (REGIA) and NPC is unclear. This study aimed to retrospectively analyze the association between REGIA expression and metastasis, radiosensitivity, and survival in patients with NPC as well as assess the effect of radiation on REGIA expression in vitro. Immunohistochemical staining was used to detect REGIA. The relationship between REGIA expression in radioresistant NPC and the prognosis of CNE1 NPC cells were analyzed using quantitative real-time polymerase chain reaction and Western blotting. We found that increased doses of radiation in CNE1 cells significantly decreased REGIA expression (P<0.05). The overall rate of REGIA-positive expression was 47.15% in NPC tissues and 45.00% and 61.02% in radiosensitive and radioresistant cases, respectively, showing significant differences (P<0.05). A REGIA-positive protein expression rate had a negative correlation with radiosensitivity in NPC (r= -0.109, P=0.047). Both REGIA-positive and REGIA-negative expression strongly predicted the overall survival rate and progression-free survival of NPC patients (P<0.01). A multivariate analysis indicated that REGIA was an inverse prognostic factor in NPC patients (REGIA-positive expression: hazard ratio (HR)=2.139, 95% confidence interval (CI)=1.56-2.94, P<0.001 and REGIA-negative expression: HR=1.958, 95% CI=1.42-2.69, P<0.001). In conclusion: Radiation can affect REGIA expression. The REGIA expression level correlated with radioresistance and a poor prognosis. In addition, REGIA expression might act as a potential therapeutic target and prognostic predictor in NPC patients.

NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans.

Using a meta-analysis framework, we investigated the association between the NLRP3 rs35829419 polymorphism and increased susceptibility to diverse diseases in humans. Relevant published studies were identified through a comprehensive and systematic electronic search, using the following scientific literature databases: Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, Chinese Biomedical, the Chinese Journal Full-Text, and the Weipu Journal. Statistical analysis of data extracted from the selected high quality studies was performed using the Version 12.0 STATA software. A total of 13 case-control studies met our stringent inclusion and exclusion criteria for the present meta-analysis. These 13 high quality studies contained relevant information on 7719 patients with various diseases and 7094 healthy controls. Our meta-analysis results showed that the NLRP3 gene rs35829419 C>A polymorphism was associated with a significantly increased risk of developing multiple diseases in humans under 5 genetic models (all P < 0.05). Data stratification and subgroup analysis based on the disease type revealed that rs35829419 C>A carriers displayed a markedly increase susceptibility to leprosy, colorectal cancer, HIV-1 infection, rheumatoid arthritis, abdominal aortic aneurysms, inflammatory bowel disease, ulcerative colitis, and atopic dermatitis. In summary, our meta-analysis results revealed the first identified strong correlation between the NLRP3 rs35829419 polymorphism and increased susceptibility to various diseases in humans.

Effects of different dietary intake on mRNA levels of MSTN, IGF-I, and IGF-II in the skeletal muscle of Dorper and Hu sheep hybrid F1 rams.

MSTN, IGF-І(insulin-like growth factor-І) and IGF-II (insulin-like growth factor-II) regulate skeletal muscle growth. This study investigated the effects of different dietary intake levels on skeletal muscles. Sheep was randomly assigned to 3 feeding groups: 1) the maintenance diet (M), 2) 1.4 x the maintenance diet (1.4M), and 3) 2.15 x the maintenance diet (2.15M). Before slaughtering the animals, blood samples were collected to measure plasma urea, growth hormone, and insulin concentrations. After slaughtering, the longissimus dorsi, semitendinosus, semimembranosus, gastrocnemius, soleus, and chest muscle were removed to record various parameters, including the mRNA expression levels of MSTN and IGFs, in addition to skeletal muscle fiber diameter and cross-sectional area. The result showed that as dietary intake improved, the mRNA expression levels of MSTN and IGF-II decreased, whereas IGF-Іexpression increased. The mRNA expression levels of MSTN and IGFs were significantly different in the same skeletal muscle under different dietary intake. The skeletal muscle fiber diameter and cross-sectional area increased with greater dietary intake, as observed for the mRNA expression of IGF-І; however, it contrasted to that observed for the mRNA expression of MSTN and IGF-II. In conclusion, dietary intake levels have a certain influence on MSTN and IGFs mRNA expression levels, in addition to skeletal muscle fiber diameter and cross-sectional area. This study contributes valuable information for enhancing the molecular-based breeding of sheep.

Effect of nutrition on plasma lipid profile and mRNA levels of ovarian genes involved in steroid hormone synthesis in Hu sheep during luteal phase.

Ovarian steroid hormones regulate follicular growth and atresia. This study aims to determine whether key ovarian sterol-regulatory genes are differentially expressed in Hu sheep under different short-term nutritional regimens. Estrus was synchronized using intravaginal progestagen sponges. The ewes were assigned randomly to 3 groups. On d 6 to 12 of their estrous cycle, the control (CON) group received a maintenance diet (1.0×M), the supplemented (SUP) group received 1.5×M, and the restricted (R) group received 0.5×M. On d 7 to 12, blood samples were taken. The sheep were slaughtered at the end of the treatment, and their organs and ovaries were collected. The plasma concentrations of urea (P<0.01), total cholesterol (P<0.01), low-density lipoprotein cholesterol (P<0.01), NEFA (P<0.01), FSH (P<0.05), and estradiol (P<0.05) increased with decreasing dietary intake, whereas plasma triglyceride (P<0.01) and triiodothyronine (T3) concentrations decreased (P<0.05). The ewes in the R group had higher spleen weight and percentage of spleen to BW and lower liver and small intestine weights and percentage of liver/stomach to BW than the SUP group ewes (P<0.05). Nutritional restriction decreased the cytochrome p450 (CYP17A1) and estrogen receptor 1 (ESR1) mRNA expression (P<0.05) and increased the cytochrome p450 aromatase (CYP19A1) mRNA expression (P<0.05) in follicles>2.5 mm. Follicle size affected the mRNA expression of very low density lipoprotein receptor (VLDLR), estrogen receptor 2 (ESR2), FSH receptor (FSHR), CYP17A1, and CYP19A1 (P<0.05). In conclusion, we suggest that a potential mechanism by which short-term negative energy balance inhibits follicular growth may involve responses to disrupted reproductive hormone concentrations and influenced the intrafollicular expression of CYP17A1, CYP19A1, and ESR1. This result may be due to increased plasma urea and lipid concentrations.

Identification of microRNAs present in congenital heart disease associated copy number variants.

PURPOSE: Congenital heart disease (CHD) is the most common congenital anomaly in newborns and about 1.35 million infants are born with CHD each year worldwide. Recently a large category of copy number variants (CNVs), were established to be a major contributor of the pathophysiology of CHD. To date most studies focused on the analysis of CNV categories or the protein coding regions without investigation on the impact of non-coding regulatory microRNAs (miRNAs). MATERIALS AND METHODS: Here with an array comparative genome hybridisation data set and a gene expression profile data set, we investigated the contribution of miRNAs in CNVs towards the development of CHD. RESULTS: Approximately 18% of the identified high frequency CNV loci were shown to harbor miRNAs. According the expression profile analysis, 52 target genes of 16 miRNAs showed association with CHD. Targets of hsa-miR-650 was reported to be enriched with genes of cardiac dysfunctions and heart failure categories previously. In the constructed network, all 12 miRNAs directly or indirectly interacts with CHD related genes and hsa-miR-570 showed the highest degree. CONCLUSIONS: Our study highlights the significance of CNV-microRNAs and their target genes in the pathogenesis of CHD. This knowledge will facilitate the identification of miRNA biomarkers and the development of new therapeutics for CHD.