Expression and significance of the polar regulation-associated protein in cholangiocarcinoma

Objective： To investigate the expressions of atypical protein kinase C = subtype （aPKC-I and E-cadherin in cholangiocarcinoma, and analyze molecular mechanisms of the invasion and metastasis of cholangiocarcinoma. Methods： The expressions of aPKC-I nd E-cadherin in 9 specimens of benign bile duct tissues and 35 specimens of cholangiocarcinoma were detected by EnVision immunohistochemistry, and their correlations to the clinicopathologic characteristics and invasion of cholangiocarcinoma were analyzed. Results： The positive rate of aPKC-I was significantly higher in cholangiocarcinoma than in benign bile duct tissues （68.6% vs. 11.1%, P = 0.006）, while the positive rate of E-cadherin was significantly lower in cholangiocarcinoma than in benign bile duct tissues （37.1% vs. 88.9%, P = 0.016）. aPKC-I expression was negatively correlated to E-cadherin expression （r = -0.287, P 〈 0.05）. aPKC-I expression was positively and E-cadherin expression was negatively correlated to the differentiation and invasion of cholangiocarcinoma （P 〈 0.05）. Conclusion： The expressions of aPKC-I and E-cadherin may reflect the differentiation and invasive potential of cholangiocarcinoma. As a polar regulation-associated protein, aPKC-I may play an important role in the invasion and metastasis of cholangiocarcinoma.

aPKC-ι和E-cadherin在胆管癌组织中的表达及意义

背景与目的:研究表明,极化调节蛋白非典型蛋白激酶C(atypical protein kinase C,aPKC)亚型aPKC-ι和E-cadherin在一些恶性肿瘤中异常表达对肿瘤的发生、发展起着重要作用。本研究分析aPKC-ι和E-cadherin在胆管癌组织中的表达与临床病理的关系,探讨胆管癌侵袭转移的分子机制。方法:采用免疫组化EnVision法检测9例非癌胆管疾病组织及35例胆管癌组织中aPKC-ι和E-cadherin表达,分析两者与胆管癌临床病理特征、侵袭性的关系。结果:aPKC-ι在胆管癌组织中的阳性高表达率为68.6%明显高于非癌胆管疾病组织的11.1%(P=0.006),E-cadherin在胆管癌中的高表达率为37.1%明显低于非癌胆管疾病组织的88.9%(P=0.016),且两者间呈负相关(r=-0.287,P<0.05);胆管癌组织分化程度、侵袭性与aPKC-ι表达呈正相关(P<0.05),与E-cadherin表达呈负相关(P<0.05)。结论:aPKC-ι和E-cadherin的表达与胆管癌分化程度和侵袭性相关,aPKC-ι可能作为一种极化调节相关蛋白在胆管癌侵袭、转移中发挥作用。

2,3,7,8-四氯二苯二噁英诱导C57BL小鼠腭裂发病机制的研究

目的探究2,3,7,8-四氯二苯二噁英(TCDD)诱导的腭裂模型中对中嵴上皮细胞影响的机制。方法E12.5孕鼠随机分为对照组和实验组,实验组孕鼠胃饲质量浓度为4μg·mL-1的TCDD;对照组孕鼠胃饲蓖麻油。于E18.5在体视显微镜下检测各组腭发育情况;分别在E13.5、E14.5、E15.5取胎鼠腭部组织行苏木精-伊红(HE)染色和免疫组织化学染色,观察小鼠腭部形态和蛋白酶活化受体/非典型蛋白激酶C(PAR/aPKC)复合物、β-连环蛋白的表达情况;用逆转录聚合酶链反应(RT-PCR)定量检测mRNA表达;Western blot定量检测PAR/aPKC复合物。结果TCDD组胎鼠在E18.5全部发生腭裂,对照组未见腭裂产生。RT-PCR定量检测,PAR/aPKC复合体mRNA在E13.5表达最强,E14.5、E15.5的表达减弱。β-连环蛋白在E14.5表达最强,E13.5次之,E15.5表达最弱;E13.5、E14.5 TCDD组β-连环蛋白的表达明显低于对照组,E15.5高于对照组(P<0.01)。Western blot检测,PAR/aPKC复合体的表达随着腭发育而降低。免疫组织化学染色显示β-连环蛋白在对照组E13.5、E14.5腭中嵴上皮细胞内呈强阳性表达。结论TCDD有可能通过干扰PAR/aPKC复合体协同β-连环蛋白参与诱导小鼠腭上皮融合异常,而导致腭裂。

Correlation of aPKC-ι and E-cadherin expression with invasion and prognosis of cholangiocarcinoma

BACKGROUND: The abnormal expression of atypical protein kinase C-ι (aPKC-ι) subtype and E-cadherin play important roles in tumor occurrence and progression This study was designed to investigate the correlation of expression of aPKC-ι and E-cadherin with the clinicopathological characteristics and prognosis of cholangiocarcinoma, and to analyze the molecular mechanisms of invasion and metastasis of the tumor. METHODS: EnVision immunohistochemistry was used to detect the expression of aPKC-ι and E-cadherin in 9 specimens of benign bile duct tissues, 35 specimens of cholangiocarcinoma and 6 specimens of metastatic cholangiocarcinoma. The relationship of the expression with clinicopathological characteristics, invasion and prognosis of cholangiocarcinoma was analyzed. A multivariate regression analysis was made of these data by the Cox proportional hazard model. RESULTS: The positive expression level of aPKC-ι in cholangiocarcinoma was remarkably higher than that in benign bile duct tissues (68.6% vs. 11.1%, P=0.006) but the expression level of E-cadherin was lower in cholangiocarcinoma than in benign bile duct tissues (37.1% vs. 88.9%, P=0.016). Correlation analysis revealed that the expression of aPKC-ι was positively related to tumor differentiation and invasion, whereas that of E-cadherin was entirely the contrary. Moreover, there wasa negative relationship between the expression of aPKC-ι and that of E-cadherin (r=-0.287, P<0.05). Univariate analysis showed that the overall survival rate of the group with a higher expression of aPKC-ι in cholangiocarcinoma was remarkably lower than that of the group with a lower expression (P<0.01); multivariate analysis revealed that the expressions of aPKC-ι and E-cadherin are important prognostic factors for cholangiocarcinoma (P<0.05). CONCLUSIONS: The expressions of aPKC-ι and E-cadherin may reflect the differentiation and invasive potential of cholangiocarcinoma. aPKC-ι and E-cadherin may be independent prognostic factors and, when used in combination with clinicopathological characteristics, may increase the accuracy in predicting the prognosis of patients with cholangiocarcinoma. As a polar regulative associated protein, aPKC-ι may play an important role in the invasion and metastasis of cholangiocarcinoma.

小分子化合物C93355对小鼠海马神经元突起的抑制作用

目的:研究小分子C93355对神经元突起生长的影响及其可能的机制。方法:培养新生小鼠海马神经元,采用免疫细胞化学染色分析神经元突起的生长,Western blot检测C93355对非典型蛋白激酶C(aPKC)的磷酸化影响。结果:小分子C93355抑制海马神经元突起的生长,降低aPKC的磷酸化。结论:小分子C93355可能通过抑制aPKC的磷酸化而调节神经元突起的生长。

非经典型蛋白激酶C的研究进展

非经典型蛋白激酶C是G蛋白偶联受体系统中的效应物,其在细胞内信号传递过程中起重要作用,可介导细胞增殖和分化、影响细胞周期和细胞凋亡、参与代谢调节、促进肿瘤形成和转移等。因此,靶向非经典型蛋白激酶C的药物在疾病治疗中有广泛的应用前景。

非典型蛋白激酶C复合物在细胞极性建立中的作用

极性是多数细胞的共同特征,是细胞分化和细胞行使正常功能的基础,细胞极性的建立对于生物体的生长发育至关重要。过去十年的研究显示,进化上保守的非典型蛋白激酶C(aPKC)复合物在许多生物的多种细胞中都参与了细胞极性的建立,并且在其中扮演着相当重要的角色,这为揭示极性建立的机制提供了重要的线索。以线虫合子前-后极(anterior-posterior)的形成、哺乳动物和果蝇上皮细胞顶-底极(apical-basal)的建立以及果蝇神经母细胞不对称分裂中细胞命运决定子的分配这3个典型的极性过程为主线,综述了aPKC复合物在细胞极性建立中的作用,并探讨其中的分子机制。

14-3-3ζ协同非典型蛋白激酶C-ι经上皮-间充质转化促进胆管癌侵袭转移

目的探讨14·3-3ζ协同非典型蛋白激酶C-ι（aPKC-ι）促进胆管癌侵袭转移的机制。方法应用免疫组织化学、Westernblot和实时定量聚合酶链反应检测14-3-3ζ和aPKC-ι在64例胆管癌组织中的表达，Kaplan—Meier和COX多因素回归分析胆管癌预后影响因素。转化生长因子-β1（TGF-β1）构建胆管癌细胞上皮．间充质转化（EMT）模型，干扰14．3．3‘或aPKC-ι的表达，检测EMT标志物的变化。抑制14-3-3ζ表达后，Transwell侵袭试验、划痕试验、克隆平板试验检测胆管癌细胞侵袭转移能力。结果14-3-3ζ和aPKC-ι在癌组织中均呈高表达（56．25％，36／64；51．56％，33／64），呈正相关（r=0．406，P=0．001）。两者低表达组的总体生存率显著高于过表达组（14-3-3ζ：X^2=10．140，P=0．001；aPKC-ι：X2：12．575，P=0．000）。14-3-3ζ和aPKC-L均是胆管癌预后的独立影响因素。干扰两者的表达抑制细胞EMT相关标志物改变，胆管癌细胞侵袭、增殖和转移能力均受到抑制。结论14-3-3ζ与aPKC-ι结合，协同促进胆管癌EMT及侵袭转移。

肝外胆管癌中aPKC-t、E-cadherin的表达及与侵袭性和预后的关系

目的研究aPKC-t和E—cadherin在肝外胆管癌中的表达与临床病理及预后的关系，探讨肝外胆管癌侵袭转移的分子机制。方法采用免疫组化EnVision法检测9例良性胆管组织、35例肝外胆管癌及6例胆管源性转移癌中aPKC-t和E—cadherin表达，分析两者与肝外胆管癌临床病理特征、预后及侵袭性的关系。应用Kaplan-Meier法计算累计生存率行单因素预后分析，并经Log-rank检验；选择可能对肝外胆管癌病人预后产生影响的临床及生物学因素进行量化，依次引入COX风险比例模型行多因素回归分析。结果在肝外胆管癌中，aPKC-t阳性表达强度明显高于良性胆管组织，E—cadherin阳性表达强度明显弱于良性胆管组织；aPKC-t表达与肝外胆管癌组织分化程度、侵袭性呈正相关，而E—cadherin表达呈负相关，aPKC-t与E—cadherin的表达经等级相关分析呈显著负相关（r=0．387，P〈0.05）；单因素生存分析显示aPKC-t高表达组的肝外胆管癌病人总生存率明显低于低表达组（P〈0.01）；多因素回归分析证实aPKC-c和E-cadherin的表达是影响肝外胆管癌病人预后的独立因素。结论aPKC-t和E-cadherin的表达与肝外胆管癌分化程度和侵袭性有关，aPKC-t和E—cadherin可作为独立的预后判断因子，结合临床病理因素能提高对肝外胆管癌病人预后判断的准确性，aPKGt作为一种极化调节相关蛋白在肝外胆管癌侵袭、转移中发挥重要作用。

Prognostic and clinical value of circPRKCI expression in diverse human cancers

Background:Highly expressed in various human cancers,circular RNA Protein Kinase C Iota(circPRKCI)has been reported to play an important role in cancer development and progression.Herein,we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.Methods:We searched the Pubmed,Web of Science,and the Cochrane Library databases from inception until May 16,2021.The relationship between circPRKCI expression and cancer patients’survival,including overall survival(OS)and disease-free survival(DFS),was assessed by pooled hazard ratios(HR)with corresponding 95%confidence interval(CI).The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios(OR)with corresponding 95%CI.The data were analyzed by STATA software(version 12.0)or Review Manager(RevMan 5.3).Results:A total of 15 studies with 1109 patients were incorporated into our meta-analysis.The results demonstrated that high circPRKCI expression was significantly related to poor OS(HR=1.96,95%CI:1.61,2.39,P<0.001)when compared with low circPRKCI expression in diverse human cancers.However,elevated circPRKCI expression was not associated with DFS(HR=1.34,95%CI:0.93,1.95,P=0.121).Furthermore,the patient with a higher circPRKCI expression was prone to have a larger tumor size,advanced clinical stage,and lymph node metastasis,but it was not significantly correlated with age,gender,and distant metastasis.Conclusion:Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features,suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.

极化调节蛋白aPKC—τ与cyclinE在肝癌中的表达及意义

目的探讨细胞极化调节蛋白aPKC—τ与CyclinE在肝细胞肝癌（HCC）及其癌旁组织中表达情况及关系。方法采用RT-PCR方法检测aPKC-τ基因在9例正常肝、43例HCC及其癌旁组织中的表达；免疫组化检测aPKC-τ,CyclinE蛋白的表达，对所得结果进行分类和统计分析。结果aPKC-τ在HCC中的基因表达值为0．844±0．315，明显高于癌旁0．530±0．217及正常肝组织0．372±0．130（P=0．009）IaPKC—τ蛋白在HCC、癌旁组织阳性率分别为58．1％（25／43）、23．6％（10／43），分化程度越低、分级越晚表达越高，表达有显著性差异（P〈0．05）；CyclinE蛋白在HCC、癌旁组织阳性率分别为65．1％（28／43）、51．6％（22／43），分化程度越低、分级越晚表达越高，表达有显著性差异（P〈O．05）；aPKC—τ蛋白的表达与CyclinE蛋白的表达呈正相关（P〈0．05）。结论aPKC-τ和CyclinE在HCC的表达提示其在HCC侵袭、转移中发挥重要作用；两者在HCC中共表达，为进一步研究肝癌侵袭转移机制提供了理论依据。

非典型蛋白激酶C的研究进展

非典型蛋白激酶C(atypical PKC,aPKC)是蛋白激酶C(protein kinase C,PKC)家族中的亚家族。aPKC具有不同于PKC家族中其他亚型的结构特征和功能特性,它在调控细胞极性建立、细胞骨架的动态组装、细胞的非对称性分裂、囊泡运输等多种生物学事件中发挥重要调控作用,从而广泛影响多种组织器官的发育及多类疾病的发生发展。aPKC的蛋白质翻译后修饰对于aPKC的激活与抑制具有重要调控作用。本文就近年来aPKC的结构、功能及蛋白质翻译后修饰的研究进展作一综述。