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Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression SCIE Scopus
期刊论文 | 2022 , 13 (9) | CELL DEATH & DISEASE
SCOPUS Cited Count: 10
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Abstract :

The mechanistic (formally "mammalian") target of rapamycin (mTOR) pathway serves as a crucial regulator of various biological processes such as cell growth and cancer progression. In bladder cancer, recent discoveries showing the cancer-promoting role of mTOR complex 1 have attracted wide attention. However, the regulation of mTOR signaling in bladder cancer is complicated and the underlying mechanism remains elusive. Here, we report that the deubiquitinating enzyme, ovarian tumor domain-containing protein 5 (OTUD5), can activate the mTOR signaling pathway, promote cancer progression, and show its oncogenic potential in bladder cancer. In our study, we found that OTUD5 deubiquitinated a RING-type E3 ligase, RNF186, and stabilized its function. In addition, the stabilization of RNF186 further led to the degradation of sestrin2, which is an inhibitor of the mTOR signaling pathway. Together, we provide novel insights into the pathogenesis of bladder cancer and first prove that OTUD5 can promote bladder cancer progression through the OTUD5-RNF186-sestrin2-mTOR axis, which may be exploited in the future for the diagnosis and treatment of this malignancy.

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GB/T 7714 Hou, Tao , Dan, Weichao , Liu, Tianjie et al. Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression [J]. | CELL DEATH & DISEASE , 2022 , 13 (9) .
MLA Hou, Tao et al. "Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression" . | CELL DEATH & DISEASE 13 . 9 (2022) .
APA Hou, Tao , Dan, Weichao , Liu, Tianjie , Liu, Bo , Wei, Yi , Yue, Chenyang et al. Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression . | CELL DEATH & DISEASE , 2022 , 13 (9) .
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Silibinin inhibits the migration, invasion and epithelial-mesenchymal transition of prostate cancer by activating the autophagic degradation of YAP SCIE
期刊论文 | 2022 , 13 (13) , 3415-3426 | JOURNAL OF CANCER
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Silibinin (SB), a flavonoid extracted from milk thistle seeds, has been found to exert antitumor effects in numerous tumor types. Our previous study reported that SB had anti-metastatic effects in prostate cancer (PCa). However, the exact underlying molecular mechanisms remain to be determined. The present study aimed to investigate the effects of SB on the migration, invasion and epithelial-mesenchymal transition (EMT) of castration-resistant PCa (CRPC) cells using wound healing, Transwell assays, and western blotting. The results revealed that SB treatment significantly inhibited the migration and invasion of CRPC cell lines. Moreover, SB was confirmed to activate autophagy, as determined using LC3 conversion, LC3 turnover and LC3 puncta assays. Further mechanistic studies indicated that the expression levels of Yes-associated protein (YAP) were downregulated in an autophagy-dependent manner after SB treatment. In addition, the SB-induced autophagic degradation of YAP was associated with the anti-metastatic effects of SB in CRPC. In conclusion, the findings of the present study suggested that SB might inhibit the migration, invasion and EMT of PCa cells by regulating the autophagic degradation of YAP, thus representing a potential novel treatment strategy for metastatic CRPC.

Keyword :

autophagy epithelial-mesenchymal transition invasion migration silibinin Yes-associated protein

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GB/T 7714 Dan, Weichao , Fan, Yizeng , Hou, Tao et al. Silibinin inhibits the migration, invasion and epithelial-mesenchymal transition of prostate cancer by activating the autophagic degradation of YAP [J]. | JOURNAL OF CANCER , 2022 , 13 (13) : 3415-3426 .
MLA Dan, Weichao et al. "Silibinin inhibits the migration, invasion and epithelial-mesenchymal transition of prostate cancer by activating the autophagic degradation of YAP" . | JOURNAL OF CANCER 13 . 13 (2022) : 3415-3426 .
APA Dan, Weichao , Fan, Yizeng , Hou, Tao , Wei, Yi , Liu, Bo , Que, Taotao et al. Silibinin inhibits the migration, invasion and epithelial-mesenchymal transition of prostate cancer by activating the autophagic degradation of YAP . | JOURNAL OF CANCER , 2022 , 13 (13) , 3415-3426 .
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ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression SCIE
期刊论文 | 2022 , 29 (8) , 1611-1624 | CELL DEATH AND DIFFERENTIATION
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The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in prostate cancer (PCa), but how SPOP functions as a tumor suppressor and contributes to PCa pathogenesis remains poorly understood. Prostate Leucine Zipper (PrLZ) serves as a prostate-specific and androgen-responsive gene, which plays a pivotal role in the malignant progression of PCa. However, the upstream regulatory mechanism of PrLZ protein stability and its physiological contribution to PCa carcinogenesis remain largely elusive. Here we report that PrLZ can be degraded by SPOP. PrLZ abundance is elevated in SPOP-mutant expressing PCa cell lines and patient specimens. Meanwhile, ERK1/2 might regulate SPOP-mediated PrLZ degradation through phosphorylating PrLZ at Ser40, which blocks the interaction between SPOP and PrLZ. In addition, we identify IL-6 might act as an upstream PrLZ degradation regulator via promoting its phosphorylation by ERK1/2, leading to its impaired recognition by SPOP. Thus, our study reveals a novel SPOP substrate PrLZ which might be controlled by ERK1/2-mediated phosphorylation, thereby facilitating to explore novel drug targets and improve therapeutic strategy for PCa.

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GB/T 7714 Fan, Yizeng , Hou, Tao , Dan, Weichao et al. ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression [J]. | CELL DEATH AND DIFFERENTIATION , 2022 , 29 (8) : 1611-1624 .
MLA Fan, Yizeng et al. "ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression" . | CELL DEATH AND DIFFERENTIATION 29 . 8 (2022) : 1611-1624 .
APA Fan, Yizeng , Hou, Tao , Dan, Weichao , Zhu, Yasheng , Liu, Bo , Wei, Yi et al. ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression . | CELL DEATH AND DIFFERENTIATION , 2022 , 29 (8) , 1611-1624 .
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Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy SCIE
期刊论文 | 2022 , 366 | CHEMICO-BIOLOGICAL INTERACTIONS
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Capsaicin (CAP), extracted from Capsicum fruits, has been reported to exhibit antitumor effects in various lines of cancer cells. However, the mechanism underlying its antitumor efficiency is not fully understood. Autophagy is a fundamental self-degradation process of cells that maintains homeostasis and plays a controversial role in tumor initiation and progression. The EMT is defined as a system regulating cells transformed from an epithelial -like phenotype into a mesenchymal phenotype by several internal and external factors, following the metastatic performance of the cells developed. The present study aimed to investigate the potential role of autophagy in CAP-induced antitumor effects in renal cell carcinoma (RCC) 786-O and CAKI-1 cell lines. The results revealed that CAP remarkably inhibited the migration and invasion of RCC cells in vitro and metastasis in vivo. Moreover, we found that the CAP treatment increased the formation of autophagolysosome vacuoles and LC3 yellow and red fluorescent puncta in RCC cells and upregulated the expression of LC3, suggesting that autophagy was induced by CAP in 786-O and CAKI-1 cell lines. Our further results demonstrated that CAP-induced autophagy was mediated by the AMPK/mTOR pathway. In conclusion, our study provides new knowledge of the potential relationship between autophagy and metastasis inhibition induced by CAP, which might be a promising thera-peutic strategy in RCC.

Keyword :

AMPK Autophagy Capsaicin Metastasis mTOR Renal cell cancer

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GB/T 7714 Que, Taotao , Ren, Bingyi , Fan, Yizeng et al. Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy [J]. | CHEMICO-BIOLOGICAL INTERACTIONS , 2022 , 366 .
MLA Que, Taotao et al. "Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy" . | CHEMICO-BIOLOGICAL INTERACTIONS 366 (2022) .
APA Que, Taotao , Ren, Bingyi , Fan, Yizeng , Liu, Tianjie , Hou, Tao , Dan, Weichao et al. Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy . | CHEMICO-BIOLOGICAL INTERACTIONS , 2022 , 366 .
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CDK12突变型前列腺癌的单中心临床病理特征分析
期刊论文 | 2021 , 14 (7) , 663-667 | 中国临床新医学
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目的 探讨细胞周期依赖性蛋白12(CDK12)突变型前列腺癌的临床病理特征、突变类型及治疗方式.方法 报告10例CDK12突变型前列腺癌患者的临床病理特征、基因检测结果和随访资料,复习相关文献并进行讨论.结果 10例患者平均确诊年龄为(66.60±6.80)岁,平均血清前列腺特异性抗原为652.19 ng/ml,并且穿刺Gleason评分均≥8分,8例患者确诊时已出现远处转移.此外,6例患者的CDK12突变发生在去势抵抗阶段.结论 CDK12突变型前列腺癌恶性程度较高且易进展至去势抵抗,该部分患者可能会从铂类化疗、聚ADP核糖聚合酶(PARP)抑制剂或免疫治疗中获益.

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GB/T 7714 樊俊杰 , 蒋凡 , 贺大林 et al. CDK12突变型前列腺癌的单中心临床病理特征分析 [J]. | 中国临床新医学 , 2021 , 14 (7) : 663-667 .
MLA 樊俊杰 et al. "CDK12突变型前列腺癌的单中心临床病理特征分析" . | 中国临床新医学 14 . 7 (2021) : 663-667 .
APA 樊俊杰 , 蒋凡 , 贺大林 , 李磊 , 谢宏俊 , 田鸽 et al. CDK12突变型前列腺癌的单中心临床病理特征分析 . | 中国临床新医学 , 2021 , 14 (7) , 663-667 .
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前列腺穿刺活检≤2针阳性患者根治术后发生Gleason评分升高的危险因素分析
期刊论文 | 2021 , 26 (3) , 226-229 | 现代泌尿外科杂志
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目的 探究超声引导下前列腺穿刺活检病理≤2针阳性患者行前列腺癌根治术(RP)后发生Gleason评分(GS)升高的相关危险因素.方法 回顾性分析2014年6月至2017年12月在西安交通大学第一附属医院泌尿外科行前列腺穿刺活检,病理诊断为≤2针阳性,且行RP的115例前列腺癌(PCa)患者的临床病理资料,采用单因素和多因素Logistic回归分析法筛选与RP后大体病理GS较术前穿刺升高的危险因素,通过受试者工作特征(ROC)曲线下面积(AUC)检验预测效能.结果 115例患者术后大体标本病理GS与术前穿刺病理相同或降低者66(57.39%)例,较术前升高者49(42.61%)例.单因素分析显示,前列腺体积(PV)、穿刺针数、穿刺阳性针数和穿刺GS差异具有统计学意义(P<0.05),将其纳入多因素Logistic回归分析,结果显示PV小(P<0.001)和穿刺阳性针数为1针(P=0.013)是RP后大体病理GS升高的独立危险因素.由PV和穿刺阳性针数预测术后GS升高的A UC为0.880,提示预测效能较好.结论 前列腺穿刺活检≤2针阳性的患者RP后病理GS较术前穿刺存在升高现象,PV较小和穿刺阳性针数为1针为其独立危险因素.

Keyword :

Gleason评分 前列腺癌 前列腺癌根治术 前列腺穿刺 前列腺活检

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GB/T 7714 时新宇 , 樊俊杰 , 王宇钊 et al. 前列腺穿刺活检≤2针阳性患者根治术后发生Gleason评分升高的危险因素分析 [J]. | 现代泌尿外科杂志 , 2021 , 26 (3) : 226-229 .
MLA 时新宇 et al. "前列腺穿刺活检≤2针阳性患者根治术后发生Gleason评分升高的危险因素分析" . | 现代泌尿外科杂志 26 . 3 (2021) : 226-229 .
APA 时新宇 , 樊俊杰 , 王宇钊 , 郭国栋 , 杨涛 , 裴昕奇 et al. 前列腺穿刺活检≤2针阳性患者根治术后发生Gleason评分升高的危险因素分析 . | 现代泌尿外科杂志 , 2021 , 26 (3) , 226-229 .
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将大学生创新性实验引入泌尿外科临床教学的探索
期刊论文 | 2021 , (3) , 95-97 | 中国高等医学教育
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医、教、研是高等医药院校及附属医院发展的三驾马车,本科教学对院校发展和人才培养至关重要.但是包括泌尿外科在内的传统临床教学存在临床前沿和课本内容脱节以及学生兴趣不高等问题.文章在分析泌尿外科传统本科教学模式缺陷的基础上,总结了将大学生创新性实验引入泌尿外科临床教学的经验,同时,提出了大学生创新性实验管理优化的办法.将大学生创新性实验引入本科临床教学,可以发挥学生的创造力和主观能动性,并提高学生的创新意识和创新能力,实现医、教、研的良性循环.

Keyword :

泌尿外科 大学生创新性实验 临床教学

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GB/T 7714 淡炜超 , 范义增 , 侯涛 et al. 将大学生创新性实验引入泌尿外科临床教学的探索 [J]. | 中国高等医学教育 , 2021 , (3) : 95-97 .
MLA 淡炜超 et al. "将大学生创新性实验引入泌尿外科临床教学的探索" . | 中国高等医学教育 3 (2021) : 95-97 .
APA 淡炜超 , 范义增 , 侯涛 , 魏怡 , 刘博 , 王子溪 et al. 将大学生创新性实验引入泌尿外科临床教学的探索 . | 中国高等医学教育 , 2021 , (3) , 95-97 .
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18F-PSMA PET/CT在前列腺癌诊断与预后预测中的价值初探
期刊论文 | 2021 , 26 (4) , 305-308 | 现代泌尿外科杂志
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目的 探讨18 F-PSMA PET/CT最大标准化摄取值(SUVmax)在前列腺癌(PCa)与增生病变的鉴别诊断,以及在PCa预后预测中的价值.方法 回顾性收集经病理证实、未经治疗的PCa同时伴有腺体增生的患者59例,治疗前行18 F-PSMA PET/CT全身显像,其中PCa灶86个,前列腺增生灶35个.比较良恶性病灶SUVmax组间差异,绘制受试者工作特性曲线(ROC),获得cut-off值.进一步根据Gleason评分对PCa灶进行分组(≤6分为低危组,=7分为中危组,≥8为高危组),比较组间SUVmax并进行事后检验分析,同时对癌灶SUVmax与Gleason评分、前列腺特异性抗原(PSA)水平进行相关性分析.结果 PCa灶的SUVmax显著高于增生灶,两组间差异具有显著统计学意义(F=27.659,P<0.001),以SUVmax 8.85作为cut-off值,ROC曲线下面积为0.843,诊断PCa的敏感性和特异性分别为69.77% 和91.43%.PCa低、中、高危组SUVmax差异无统计学意义(F=1.857,P=0.163),事后检验两两组间均未见统计学差异(P=0.744,P=0.191,P=0.075).此外,PCa灶SUVmax与Gleason评分、PSA之间差异均无统计学意义(P=0.248,P=0.101,P=0.064).结论 初步研究显示,18 F-PSMA PET/CT SUVmax对前列腺病变良恶性鉴别具有较高价值,以SUVmax 8.85作为cut-off值可获得较为理想的诊断效能.对于PCa分级及预后预测,18 F-PSMA PET/CT SUVmax价值有限.

Keyword :

18F-PSMA PET/CT SUVmax 鉴别诊断 前列腺癌 预后预测

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GB/T 7714 王卓楠 , 吴开杰 , 郑安琪 et al. 18F-PSMA PET/CT在前列腺癌诊断与预后预测中的价值初探 [J]. | 现代泌尿外科杂志 , 2021 , 26 (4) : 305-308 .
MLA 王卓楠 et al. "18F-PSMA PET/CT在前列腺癌诊断与预后预测中的价值初探" . | 现代泌尿外科杂志 26 . 4 (2021) : 305-308 .
APA 王卓楠 , 吴开杰 , 郑安琪 , 高俊刚 , 袁网 , 李磊 et al. 18F-PSMA PET/CT在前列腺癌诊断与预后预测中的价值初探 . | 现代泌尿外科杂志 , 2021 , 26 (4) , 305-308 .
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三维质量评价模式对前列腺癌术后尿失禁患者控尿功能及生活质量的影响
期刊论文 | 2021 , 46 (9) , 1054-1058 | 贵州医科大学学报
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目的 探讨三维质量评价模式对前列腺癌术后尿失禁患者控尿功能及生活质量的影响.方法 根据术后管理模式将76例前列腺癌术后尿失禁患者均分为对照组和观察组,对照组采用常规术后管理模式、观察组采用三维质量评价管理模式;于管理模式实施前及实施1月时,采用自尊量表(SES)、生活质量量表(SF-36)分别评估2组患者的自尊程度及生活质量,并检测2组患者的血清皮质醇(Cor)水平;于管理模式实施2周时,比较2组患者模式实施2周时的尿控有效率.结果 管理模式实施1月时,2组患者SES、SF-36评分均高于实施前,观察组高于对照组,差异有统计学意义(P<0.05);模式实施2周时,观察组患者的控尿有效率高于对照组,差异有统计学意义(P<0.001);模式实施前,2组患者血清Cor水平比较,差异无统计学意义(P>0.05);模式实施1月时,2组患者血清Cor水平均升高,且观察组低于对照组,差异有统计学意义(P<0.001).结论 三维质量评价管理模式可以有效改善前列腺癌术后尿失禁患者自尊程度、控尿功能及生活质量,下调血清Cor水平.

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GB/T 7714 樊荣 , 蒋玉梅 , 李磊 et al. 三维质量评价模式对前列腺癌术后尿失禁患者控尿功能及生活质量的影响 [J]. | 贵州医科大学学报 , 2021 , 46 (9) : 1054-1058 .
MLA 樊荣 et al. "三维质量评价模式对前列腺癌术后尿失禁患者控尿功能及生活质量的影响" . | 贵州医科大学学报 46 . 9 (2021) : 1054-1058 .
APA 樊荣 , 蒋玉梅 , 李磊 , 高慧敏 . 三维质量评价模式对前列腺癌术后尿失禁患者控尿功能及生活质量的影响 . | 贵州医科大学学报 , 2021 , 46 (9) , 1054-1058 .
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双镜联合同期处理肾盂输尿管连接部梗阻合并肾盏结石14例报告
期刊论文 | 2021 , 26 (5) , 422-424,447 | 现代泌尿外科杂志
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目的 总结我院泌尿外科应用腹腔镜联合输尿管软镜技术同期治疗肾盂输尿管连接部梗阻(U PJO)合并继发肾盏结石的临床经验.方法 回顾性收集2019年1月至2020年3月实施经腹腔途径腹腔镜肾盂成形术同期行输尿管软镜碎石取石术的14例患者的临床资料,分析结石大小、数目、手术时间、手术并发症及结石成分等指标.结果 左侧病例9例,右侧5例,术前通过磁共振尿路成像(M RU)、逆行肾盂造影及C T检查明确为U PJO合并继发肾盏结石,积水为中度到重度.所有手术均同期完成,其中2例有残余结石.所有病例均无副损伤及中转开放;术中发现结石为1~15块,直径2~25 mm;手术时间130~270 min,平均(180±36)min;术中出血量20~100 mL,围手术期均未输血.术后均无漏尿发生,所有患者均顺利恢复,术后3~5 d拔除引流管,术后住院3~6 d(平均4 d),术后6~8周行膀胱镜拔除双J管,复查肾积水均明显缓解.病例随访6~21个月,随访期内肾积水无加重.结论 经腹腹腔镜联合输尿管软镜技术治疗U PJO合并继发肾盏结石安全有效,且创伤小、出血少、清石率高,是U PJO合并继发结石患者的较好选择,值得临床推广应用.

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GB/T 7714 陈炜 , 张盼 , 何辉 et al. 双镜联合同期处理肾盂输尿管连接部梗阻合并肾盏结石14例报告 [J]. | 现代泌尿外科杂志 , 2021 , 26 (5) : 422-424,447 .
MLA 陈炜 et al. "双镜联合同期处理肾盂输尿管连接部梗阻合并肾盏结石14例报告" . | 现代泌尿外科杂志 26 . 5 (2021) : 422-424,447 .
APA 陈炜 , 张盼 , 何辉 , 龙清志 , 李翔 , 王迎 et al. 双镜联合同期处理肾盂输尿管连接部梗阻合并肾盏结石14例报告 . | 现代泌尿外科杂志 , 2021 , 26 (5) , 422-424,447 .
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