Function and regulatory mechanism of androgen receptor variant 7 in castration resistant prostate cancer / 中华泌尿外科杂志

Androgen receptor (AR) plays a key regulatory role in the development of castration resistant prostate cancer (CRPC), and the level of constitutive active variants represented by androgen receptor variant 7 (AR-V7) is increasing during the progress of CRPC, which can be used as a molecular marker of disease progress and prognosis of patients with CRPC. It is an important target to overcome castration resistance and improve the quality of life and survival of patients. In this paper, the function of AR-V7 and its molecular regulation mechanism in CRPC are reviewed. The research shows that the generation of AR-V7 is related to the structural rearrangement of AR gene, gene amplification and the selective splicing of AR gene transcripts, and it is affected by the coordinated regulation of multiple signal pathway molecules such as TGF-β; AR-V7 changes the transport and nuclear localization mechanism of AR protein, and further affects the transcriptional expression of downstream target genes. AR-V7 antagonizes AR activity and blocks the differentiation process driven by AR and androgen, and inhibits the expression of tumor suppressor genes to stimulate the proliferation of tumor cells, thus promoting the progress of Pca. Related targeting studies have revealed AR-V7 targets and CRPC treatment strategies. Currently, they mainly focus on AR-V7 protein degradation, mRNA expression inhibition and N-terminal domain targeting intervention. With the development of in-depth research, the molecular mechanism of AR-V7 in the progress of Pca will be gradually clarified, which will certainly play a greater role in the prevention and treatment of CRPC.

Research progress in the relationship between deubiquitinase OTUB1 and urological cancer / 国际生物医学工程杂志

Ovarian tumor-associated protease B1(OTUB1) is a member of the deubiquitinase family. Its highly specific recognition and cleavage function of polyubiquitinated chains has attracted widespread attention, and it can regulate a variety of important signaling pathways, such as the epithelial-mesenchymal transition (EMT) pathway, the MAPK signaling pathway, and the p53-related signaling pathway. In recent years, it has gradually become a new direction of oncology research. More and more studies have proved that OTUB1 is closely related to various tumors such as hepatocellular carcinoma, colorectal cancer, and breast cancer. It regulates the occurrence, development, and prognosis of tumors. OTUB1 could be a potential treatment for tumors. Urinary tract tumors mainly include prostate cancer, bladder cancer, and renal cell carcinoma. In this review, the research progress on the correlation between OTUB1 and urological tumors was reviewed, including its important role in the occurrence and development of urological tumors and the possibility of treating urological tumors with OTUB1.

Screening of variation in the promoter of PPARGC1A gene and study of its association with the risk of type 2 diabetes in ethnic Hans from Beijing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM).</p><p><b>METHODS</b>A 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCRRFLP in a small population (n=216, T2DM/control: 104/112), which was followed by a replication study of a larger group (n=1546, T2DM/control: 732/814). Fasting plasma glucose, insulin, blood lipid, height, weight, waist circumference, and blood pressure were measured in all subjects. Potential association was assessed by logistic regression. Linkage disequilibrium and haplotype analysis were conducted with Haploview software.</p><p><b>RESULTS</b>Five polymorphisms were identified with Sanger sequencing, among which T-2120C (rs3755857), -1999C/G (rs2946386) and -1437T/C (rs2970870) were included for genotypic analysis based on their moderate levels of heterozygosity. No significant difference was found between the two groups. When adjusted for age and gender confounding, we have combined the OR values from population 1 and population 2 based on Mantel-Haenszel fixed model, and recognized a mild contribution of C allele of -1999C/G (rs2946386) to the 1.18-fold risk of T2DM (P=0.03, OR=118). No haplotype was associated with T2DM after permutation correction.</p><p><b>CONCLUSION</b>The C allele of -1999C/G ( rs2946386) in the promoter region of the PPARGC1A gene is mildly associated with T2DM. Variations in the promoter region of the PPARGC1A gene seem not to confer the risk of T2DM in our population.</p>

Changes in the expression of bone morphogenetic protein 7 and tamm-horsfall protein in the early stages of diabetic nephropathy

Bone morphogenetic protein 7 [BMP7]has been suggested to play a protecOriginal Article tive role against kidney injury in chronic kidney disease. To identify the critical molecular regulators in the early stage of diabetic ne-phropathy, we studied the expression of BMP? and 2 important kidney-specific markers, podocin and Tamm-Horsfall protein [THP]. A diabetic nephropathy model was established by intraperitone-ally injecting streptozotocin [STZ] in male Kunming mice. Kidney weight index was used as an indicator of early renal injury. Kidney tissue from the diabetic model mice was obtained at 4, 8, and 12 weeks, and total protein was extracted to assess the expression of BMP?, podocin, and THP by western blot analysis. Diabetic model mice were successfully established, and the kidney weight index of the model animals increased significantly. The expression of BMP? was significantly downregulated, while the expression of THP was increased in the early stage of diabetic nephropathy. However, the expression of podocin did not change. Our observations suggested that down-regulation of BMP? expression and up-regulation of THP expression were early events that occur prior to podocyte injury with the structure protein, podocin spoiled, which further confirmed that BMP? is a key molecular regulator in the early stage of diabetic nephropathy