前列腺癌发生风险与CYP3A5基因多态性的关系

目的 探讨CYP3A5基因多态性与前列腺癌发生风险和病理特点的关系。方法 采用限制性片段多态性分析法对356例前列腺癌患者和306个男性对照中CYP3A5基因第3内含子多态性进行了研究。结果 在前列腺癌和对照组之间CYP3A5基因型分布差异无显著性(P=0．063)，但两组间CYP3A5*1等位基因的分布差异存在显著性(P=0．025)；与携带CYP3A5*3*3基因型者相比，携带CYP3A5*1等位基因的男性患前列腺癌的风险降低了30％(P=0．026)。在不同分期和分级的前列腺癌患者之间CYP3A5基因型分布差异无显著性(P=0．904和0．986)。结论 CYP3A5基因中的CYP3A5*1等位基因可能与前列腺癌的患病风险降低有关。     

CYP1A2基因多态性与前列腺癌的相关性研究

目的:评价CYP1A2基因单核苷酸多态性(SNPs)与前列腺癌分期分级的相关性。方法:对253例良性前列腺增生(BPH)患者与206例去势前列腺癌患者CYP1A2基因中rs2069514-3859(A>G)位点及rs2069525-1707(C>T)位点进行基因测序,并对各基因表型与前列腺癌的分期分级相关性进行统计学分析。结果:BPH及去势前列腺癌患者的两种CYP1A2单核苷酸多态性的发生率无明显差异(P>0.05),其基因多态性与前列腺癌的病理分期均无相关性(P>0.05);但rs2069525-1707(C>T)中含C等位基因型的前列腺癌Gleason评分多在7分以下(P=0.030,OR=4.658,95%CI:1.222～17.754)。结论:CYP1A2基因的SNPs与前列腺癌的病理分级之间可能有一定的相关性,但其发生机制及临床意义有待进一步证实及研究。     

同源框基因NKX3．1与前列腺发生及前列腺癌的关系

同源框基因是一类含有同源序列的基因，其编码的蛋白质参与基因转录水平的调控，进而调节细胞的发育和分化，在胚胎形成过程中扮演重要角色，NKX3．1是新近发现的同源模型框基因，在胚胎期参与前列腺的发生和分化，并参与维持前列腺细胞的功能和细胞对雄性激素依赖性的形成，进一步的研究发现，NKX3．1可能为前列腺癌发生的特异性抑癌基因。     

SLC5A8基因转录沉默与乳腺癌

目的 探讨乳腺癌发生过程中的SLC5A8基因转录沉默现象.方法 回顾性分析2014年6月-2015年6月河北大学附属医院基本外科收治的32例乳腺癌患者的病例资料,分析术中采集的乳腺癌组织及癌旁组织标本,采用实时荧光定量聚合酶链式反应法检测两组标本中SLC5A8基因的转录水平.应用配对t检验和x2检验的方法分析结果.结果 癌组织SLC5A8基因mRNA转录水平显著低于癌旁组织(P＜0.05).乳腺癌组织中有20例(62.5％) SLC5A8基因无转录产物.癌旁组织标本中仅有4例(12.5％) SLC5A8无基因转录产物.癌组织的SLC5A8的失活率显著高于癌旁组织(P＜0.05).结论 SLC5A8基因转录沉默是乳腺癌发生过程中的重要事件.     

睾酮5-α还原酶Ⅱ基因V89L多态性与前列腺癌预后关系的研究

目的:探讨睾酮5-α还原酶Ⅱ(SRD5A2)基因V89L多态性与影响前列腺癌预后因素的关系。方法:对V89L多态性位点用Rsa-1限制性内切酶进行酶切鉴定,观察112例前列腺癌患者和89例BPH患者的V89L(VV、VL、LL)多态性分布情况的差异及其多态性与前列腺癌患者年龄、前列腺特异性抗原(PSA)、游离PSA/总PSA值(tPSA/fPSA,F/T)、Gleason评分、临床分期的关系。结果:前列腺癌组112例与BPH组89例的V89L基因频度风险无显著性差异(χ2=3.606,df=2,P=0.165)。前列腺癌组VV和VL+LL基因型与fPSA、tPSA、F/T、T分期、Gleason评分差异无显著性(P>0.05)。VV和VL+LL各评价预后指标差异无显著性(P>0.05)。分段评价PSA水平、Gleason评分、临床分期、年龄,均与两种基因型无相关性(P>0.05)。结论:V89L多态性与预后无明显关系,但是可能与前列腺癌的风险存在间接的关系。     

睾酮5-α还原酶Ⅱ基因多态性与影响前列腺癌预后素关系的研究

目的探讨睾酮5-α还原酶Ⅱ(SRD5A2)基因多态性与影响前列腺癌预后因素的关系.方法对112例前列腺癌患者(前列腺癌组)与89例前列腺增生患者(前列腺增生组)的SRD5A2基因89密码子亮氨酸替代缬氨酸(V89L)及49密码子苏氨酸替代丙氨酸(A49T)多态性位点进行酶切鉴定,了解V89L及A49T基因多态性分布情况的差异,及基因多态性与前列腺癌患者的年龄、血游离前列腺特异抗原(PSA)、总PSA、游离PSA/总PSA值、Gleason评分、临床分期的关系.结果前列腺癌组与前列腺增生组V89L和A49T基因频度风险无显著性差异(分别为0.040与0.045,0.308与0.399,χ2值为0.047、3.606,P均>0.05).前列腺癌组AT+TT基因型患者的发病年龄[(65±9)岁]明显低于AA基因型者[(71±7)岁](P=0.03),Gleason评分平均水平明显高于AA基因型(P=0.015).VV和VL+LL基因型各评价预后指标差异无显著性.分段评价PSA水平、Gleason评分、临床分期、年龄,均与两种基因型无相关性.结论 AT+TT基因型前列腺癌患者的预后可能较差, VL+LL基因型与预后无明显关系.     

9-顺维甲酸对前列腺癌细胞系LNCaP中同源盒基因NKX3.1表达的影响(英文)

目的:研究9-顺维甲酸对前列腺癌细胞系 LNCaP 中同源盒基因 NKX3.1表达的调节作用。方法:采用流式细胞术、反转录 PCR 和 Western Blot 技术检测9-顺维甲酸对 LNCaP 细胞周期及 NKX3.1表达的影响;构建和转染 NKX3.1启动子-报告基因质粒及其缺失突变体,通过报告基因活性测定,鉴定 NKX3.1启动子中受9顺-维甲酸调控的区域。结果:通过转染及报告基因检测,发现9-顺维甲酸在 LNCaP 细胞中可明显提高 NKX3.1启动子的活性:RT-PCR 和 Western Blot 结果显示,9-顺维甲酸可提高 NKX3.1mRNA 和蛋白的表达,并呈剂量依赖性;通过启动子缺失突变分析,发现 NKX3.1基因上游-936至-921区明显受9-顺维甲酸诱导调节;流式细胞术分析细胞周期的结果显示,9-顺维甲酸可阻止 LNCaP 细胞于 G_1期,减少 G_2/M 期细胞。结论:9-顺维甲酸作为诱导分化剂可阻止 LNCaP 细胞于 G_1期,减少细胞有丝分裂,并明显上调前列腺特异的抑癌基因 NKX3.1的表达。     

睾酮5-α还原酶Ⅱ基因A49T多态性与影响前列腺癌预后关系的研究

目的探讨睾酮5-α还原酶Ⅱ（SRD5A2）基因A49T（49密码子苏氨酸替代丙氨酸）多态性与影响前列腺癌预后因素的关系。方法对A49T多态性位点用Mwo-1限制性内切酶进行酶切鉴定,观察112例前列腺癌患者和89例前列腺增生患者的A49T三种不同基因型（AA、AT、TT）多态性分布情况的差异及其多态性与前列腺癌患者年龄、前列腺特异性抗原（PSA）、游离PSA／总PSA值（F／T）、Gleason评分、临床分期的关系。结果前列腺癌组与前列腺增生组的A49T基因频度风险无显著性差异（P〉0．05）。AT＋TT基因型患者发病年龄明显低于AA型（P〈0．05）。AT＋TT基因型患者Gleason评分平均水平明显高于AA型（P〈0．05）。AT＋TT基因型可能预后较差。用分段评价PSA、Gleason评分、TNM分期、年龄均与两种基因型无相关性,提示基因型与预后无显著性差异。AA、AT＋TT基因型与Gleason评分的关系,等级评分（2～10分）与分段评价法（≤6分、〉6分）结果不一致。结论用等级评分与分段评价法结果不一致。等级评分法比分段法或许更能反映Gleason评分与A49T基因型的关系,更适用于估计预后。     

同源框基因NKX3.1 mRNA和蛋白在前列腺组织特异性表达及与前列腺癌关系的探讨

目的:分析同源框基因NKX3.1 mRNA和蛋白在国人前列腺组织表达状况以及与前列腺癌关系。方法:采用半定量RT-PCR、蛋白杂交和免疫组化检测76例前列腺组织、96例非前列腺组织标本NKX3.1 mRNA和蛋白表达状况。结果:RT-PCR检测显示76例前列腺组织NKX3.1 mRNA表达率98.7%,96例非前列腺组织标本中,除2例睾丸组织、1例乳腺组织有NKX 3.1表达外,其余肾脏、膀胱、肝脏、回肠、脂肪、皮肤组织无1例表达(P<0.01)。蛋白杂交显示NKX 3.1蛋白总阳性表达率前列腺组织为100%,睾丸、乳腺组织均为16.7%,膀胱、回肠组织为8.3%,其他肾脏、肝脏、脂肪和皮肤组织均为0(P<0.01)。免疫组化检测显示NKX3.1蛋白主要分布在前列腺上皮细胞,上皮细胞总阳性表达率为94.7%,间质细胞NKX3.1蛋白总阳性表达率为5.3%;NKX3.1蛋白强阳性表达率良性前列腺组织为13.6%,前列腺癌组为40.6%(P<0.01)。结论:NKX3.1基因不仅为前列腺器官特异性基因,并且可能是前列腺腺上皮细胞特异性基因,其表达与前列腺癌关系密切。     

CYP3A4*1G和CYP3A5*3基因多态性对颌面外科手术患者舒芬太尼代谢的影响

目的:研究CYP3A4*1G和CYP3A5*3基因多态性相互作用对颌面外科手术患者舒芬太尼药物代谢的影响.方法:选取2018年10月-2019年12月在西安交通大学口腔医院颌面外科择期全麻下行颌面外科手术的88例患者为研究对象,年龄21～69岁,根据美国麻醉医师学会(ASA)分级为ASA Ⅰ或Ⅱ级.采用聚合酶链(PCR...     

CircRNA pappalysin 1 facilitates prostate cancer development through miR-515-5p/FKBP1A axis

The role of circular RNA (circRNA) pappalysin 1 (circ-PAPPA; hsa_circ_0088233) in prostate cancer (PCa) cells was explored in the current study. Circ-PAPPA abundance was markedly enhanced in PCa. Circ-PAPPA interference restrained cell viability, proliferation, motility and glycolysis while elevated the apoptosis rate of PCa cells. Circ-PAPPA negatively regulated microRNA-515-5p (miR-515-5p) abundance. MiR-515-5p silencing largely diminished circ-PAPPA knockdown-mediated effects in PCa cells. MiR-515-5p directly bound to FKBP prolyl isomerase 1A (FKBP1A). MiR-515-5p overexpression-mediated impacts were partly counteracted by FKBP1A overexpression. Circ-PAPPA silencing reduced FKBP1A protein level partly by elevating miR-515-5p expression. Circ-PAPPA knockdown significantly restrained the tumour growth in vivo. Circ-PAPPA elevated the malignant phenotypes of PCa cells by sequestering miR-515-5p to induce the expression of FKBP1A.     

Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer

BACKGROUND: The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS: Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS: Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the "T" allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS: Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.     

Prevalence of hypouricaemia and SLC22A12 mutations in healthy Korean subjects

Aim: Mutations in the SLC22A12 gene, which encodes a uric acid transporter, URAT1, are associated with renal hypouricaemia. This study was designed to measure serum uric acid (Sua) levels and allele frequencies of two common mutations in SLC22A12, W258X and R90H, in healthy Korean subjects. Methods: A total of 909 unrelated Korean adults (male : female, 1:1.23; mean age, 48.4 ± 11.0 years) were recruited among those who had taken a routine health check-up in a health centre in 2003. None of them had hypertension, diabetes mellitus, kidney diseases or liver diseases. Genotyping for W258X and R90H was performed using the TaqMan method. Results: The prevalences of hyperuricaemia (Sua levels, >416 µmol/L) and hypouricaemia (Sua levels, <178 µmol/L) were 4.6% and 3.3%, respectively. A marked male preponderance in the hyperuricaemic group was noted, and the men revealed higher Sua than the women. The Sua showed a positive correlation with serum creatinine level and blood pressure. In the hypouricaemic group, the allele frequencies of W258X and R90H were 11.7% and 6.7%, respectively, and the proportion of subjects with one or both of the mutant alleles was 33.3%. Hyperuricaemic subjects never had either mutation. Conclusion: The W258X and/or R90H mutations in the SLC22A12 gene are one of the major factors responsible for hypouricaemia, and one-third of the hypouricaemic subjects had one or both of the mutant alleles.     

MiR-129-5p/DLX1 signalling axis mediates functions of prostate cancer during malignant progression

We mainly corroborated the potential mechanism of DLX1 and miR-129-5p in prostate cancer cells. DLX1 was upregulated in cancer cells according to qRT-PCR assay. We evaluated the functional changes of the transfected cells via Transwell assay, CCK-8 assay and wound healing assay. DLX1 was confirmed as a cancer promoter. In addition, qRT-PCR showed down-regulated miR-129-5p expression in prostate cancer. We further used dual-luciferase reporter detection to elucidate the targeting between these two genes. The inhibition of miR-129-5p on tumour was verified. Besides, co-transfection of oe-DLX1 and miR-129-5p mimics attenuated this inhibition. These data demonstrated functions of DLX1/miR-129-5p axis in prostate cancer: miR-129-5p hindered the biological functions of cancer cells via inhibiting DLX1 expression. We provide a novel biomarker for prostate cancer.     

SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness

BACKGROUND: Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk. METHODS: Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles. RESULTS: The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7). CONCLUSIONS: In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism.