BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC ...BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.展开更多
Background::Non-coding RNAs have attracted considerable attention for their vital role in cancer.The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma(HCC)and reveal the...Background::Non-coding RNAs have attracted considerable attention for their vital role in cancer.The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma(HCC)and reveal their regulatory mechanism in the pathophysiological process.Methods::We measured the expression of mucin 1(MUC1)and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot,screened for aberrantly expressed microRNAs(miRNAs)by miRNA microarrays.Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1,which were validated by RNA immunoprecipitation assay and luciferase reporter assay.Cell counting kit-8,Transwell assays,and flow cytometry were used to conduct functional experiments.Proteins were examined by western blot and immunohistochemical staining assays.Significant differences between groups were estimated using the one-way analysis of variance.A P<0.05 was considered statistically significant.Results::MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues(normal vs.tumor,1.007±0.215 vs.75.213±18.403,t=18.401,P<0.001)while miR-485-5p was down-regulated(normal vs.tumor,4.894±0.684 vs.1.586±0.398,t=16.191,P<0.001).Inhibition of miR-485-5p promoted cell proliferation(73.33%±5.13%vs.41.33%±3.51%,t=8.913,P<0.001),migration(102±8 cells vs.46±8 cells,t=8.681,P<0.001),invasion(59±7 cells vs.28±2 cells,t=8.034,P<0.01),and suppressed apoptosis(22.64%±6.97%vs.36.33%±3.96%,t=2.958,P<0.05)of HepG2 cells with which MUC1 is knocked down.Mechanically,miR-485-5p binds to MUC1,while circHECTD1 binds to miR-485-5p,resulting in the indirect up-regulation of the MUC1 level.Conclusions::Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.展开更多
目的通过Meta分析探讨甲状腺癌组织中黏蛋白1(MUC1)表达的临床意义及其与各临床病理参数的相关性。方法检索维普、万方、中国知网、中国生物医学文献、PubMed、Web of Science、Embase、Cochrane中英文数据库中关于MUC1在甲状腺癌中表...目的通过Meta分析探讨甲状腺癌组织中黏蛋白1(MUC1)表达的临床意义及其与各临床病理参数的相关性。方法检索维普、万方、中国知网、中国生物医学文献、PubMed、Web of Science、Embase、Cochrane中英文数据库中关于MUC1在甲状腺癌中表达及其意义的文献,以比值比(OR)和95%置信区间(95%CI)为效应指标,采用STATA 14软件进行Meta分析,并对发表偏倚及敏感性进行检验。结果共纳入13项病例对照研究,甲状腺癌病例组共1157例,非甲状腺癌对照组共509例。结果显示,甲状腺癌病例组MUC1表达明显高于非甲状腺癌对照组(OR=9.78,95%CI:7.49~12.78,P<0.001);伴有淋巴结转移的甲状腺癌组织中MUC1表达高于无淋巴结转移的甲状腺癌组织(OR=3.08,95%CI:1.37~6.92,P<0.05);TNM分期为Ⅲ~Ⅳ期的甲状腺癌组织中MUC1表达高于TNM分期为Ⅰ~Ⅱ期的甲状腺癌组织(OR=1.88,95%CI:1.22~2.90,P<0.05)。结论与非甲状腺癌对照组比较,甲状腺癌病例组MUC1呈高表达,且MUC1高表达与淋巴结转移、TNM分期密切相关。MUC1与甲状腺癌的发生和发展存在相关性,有望成为甲状腺癌分子研究领域的一项新靶标。展开更多
Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collect...Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.展开更多
目的·探究黏蛋白1(mucin 1,MUC1)调控肿瘤细胞增殖、迁移和干性维持的功能位点。方法·通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析寻找MUC1基因在不同癌症中的突变特征,对不同MUC1突变位点进行分析及定位,...目的·探究黏蛋白1(mucin 1,MUC1)调控肿瘤细胞增殖、迁移和干性维持的功能位点。方法·通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析寻找MUC1基因在不同癌症中的突变特征,对不同MUC1突变位点进行分析及定位,并按突变出现频率排序;通过Western blotting筛选出突变频率较高且蛋白稳定表达的MUC1突变体,利用乳腺癌细胞株BT549敲除MUC1细胞系和乳腺非转化细胞株MCF-10A,应用慢病毒表达系统构建MUC1野生型(MUC1-WT)和突变体稳定表达的细胞系。采用免疫荧光法检测不同MUC1突变体的细胞定位。以MUC1-WT为阳性对照、MUC1-AQA功能丧失突变体为阴性对照,对不同突变细胞的肿瘤生物学功能进行分析:通过细胞计数试剂盒-8(cell counting kit-8,CCK-8)及克隆形成实验检测细胞增殖能力;通过划痕实验及Transwell实验检测细胞迁移能力;通过成球实验检测细胞干性。使用PyMOL软件分析MUC1突变体结构定位并通过蛋白质对接软件(ZDOCK Server)进行分子对接分析。结果·在TCGA数据库中得到102个位于MUC1编码区的突变,其中P418S、S251R、V359I、N271S、N465H 5个错义突变出现频率较高且位于非数目可变串联重复序列(non-variable number of tandem repeats,non-VNTR)区域。进一步检测发现MUC1-S251R、N271S、V359I突变体可稳定表达;细胞定位分析发现这3个突变体主要分布于细胞质,同时细胞核也有一定的分布,核质比与野生型未见明显差异。表达不同MUC1突变体细胞的肿瘤生物学功能分析发现:①MUC1-WT高表达显著增强BT549和MCF-10A细胞的增殖能力;与MUC1-WT细胞相比,MUC1-AQA、S251R、N271S突变体细胞增殖能力下降,但MUC1-V359I突变体细胞与MUC1-WT细胞具有相似的增殖能力。②MUC1-WT高表达细胞的迁移能力显著增强,而MUC1-AQA细胞迁移能力减弱。在BT549细胞中,MUC1-S251R与MUC1-V359I突变体细胞迁移能力与MUC1-WT细胞相似,但MUC1-N271S细胞的迁移能力较MUC1-WT细胞降低。在MCF-10A细胞中,MUC1-N271S与MUC1-V359I细胞的迁移能力接近MUC1-WT细胞;但MUC1-S251R细胞较MUC1-WT细胞迁移能力显著下降。③MUC1-WT高表达显著增强2种细胞的干性,而MUC1-AQA细胞干性丧失;MUC1-N271S、V359I与MUC1-WT具有相似的维持细胞干性的能力,而MUC1-S251R使细胞干性减弱。PyMOL软件分析结果显示,MUC1-N271S及V359I位于海胆精子蛋白-肠激酶-聚集蛋白(sperm protein-enterokinase-agarin,SEA)区域及附近,分别处于loop区及β-折叠处;分子对接结果显示,MUC1-WT及V359I与表皮生长因子受体(epidermal growth factor receptor,EGFR)胞外域形成复合物的稳定性强于MUC1-N271S和S251R,其稳定性排序为V359I>WT>N271S>S251R。结论·MUC1突变体对肿瘤细胞的生物学功能具有不同影响,其对增殖能力影响可能与EGFR信号通路相关。MUC1-V359I与MUC1-WT相似,并未影响MUC1对肿瘤细胞增殖、迁移及干性维持的作用;而MUC1-S251、N271位点可能参与细胞增殖和迁移的信号通路调控且MUC1-S251位点对维持细胞干性较为重要。展开更多
Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response wa...Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.展开更多
基金Suzhou Science and Technology Program,No.SLT202005Suzhou Municipal Commission of Health and Family Planning,No.LCZX202031+1 种基金Suzhou New District Science and Technology Plan,No.2019Z009Independent Innovation Project of National High Tech Development Zone Hospital,No.SGY2018C03.
文摘BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.
基金a grant from the Medical Health Science and Technology Program of Zhejiang Province(No.2019PY003).
文摘Background::Non-coding RNAs have attracted considerable attention for their vital role in cancer.The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma(HCC)and reveal their regulatory mechanism in the pathophysiological process.Methods::We measured the expression of mucin 1(MUC1)and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot,screened for aberrantly expressed microRNAs(miRNAs)by miRNA microarrays.Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1,which were validated by RNA immunoprecipitation assay and luciferase reporter assay.Cell counting kit-8,Transwell assays,and flow cytometry were used to conduct functional experiments.Proteins were examined by western blot and immunohistochemical staining assays.Significant differences between groups were estimated using the one-way analysis of variance.A P<0.05 was considered statistically significant.Results::MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues(normal vs.tumor,1.007±0.215 vs.75.213±18.403,t=18.401,P<0.001)while miR-485-5p was down-regulated(normal vs.tumor,4.894±0.684 vs.1.586±0.398,t=16.191,P<0.001).Inhibition of miR-485-5p promoted cell proliferation(73.33%±5.13%vs.41.33%±3.51%,t=8.913,P<0.001),migration(102±8 cells vs.46±8 cells,t=8.681,P<0.001),invasion(59±7 cells vs.28±2 cells,t=8.034,P<0.01),and suppressed apoptosis(22.64%±6.97%vs.36.33%±3.96%,t=2.958,P<0.05)of HepG2 cells with which MUC1 is knocked down.Mechanically,miR-485-5p binds to MUC1,while circHECTD1 binds to miR-485-5p,resulting in the indirect up-regulation of the MUC1 level.Conclusions::Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.
文摘目的通过Meta分析探讨甲状腺癌组织中黏蛋白1(MUC1)表达的临床意义及其与各临床病理参数的相关性。方法检索维普、万方、中国知网、中国生物医学文献、PubMed、Web of Science、Embase、Cochrane中英文数据库中关于MUC1在甲状腺癌中表达及其意义的文献,以比值比(OR)和95%置信区间(95%CI)为效应指标,采用STATA 14软件进行Meta分析,并对发表偏倚及敏感性进行检验。结果共纳入13项病例对照研究,甲状腺癌病例组共1157例,非甲状腺癌对照组共509例。结果显示,甲状腺癌病例组MUC1表达明显高于非甲状腺癌对照组(OR=9.78,95%CI:7.49~12.78,P<0.001);伴有淋巴结转移的甲状腺癌组织中MUC1表达高于无淋巴结转移的甲状腺癌组织(OR=3.08,95%CI:1.37~6.92,P<0.05);TNM分期为Ⅲ~Ⅳ期的甲状腺癌组织中MUC1表达高于TNM分期为Ⅰ~Ⅱ期的甲状腺癌组织(OR=1.88,95%CI:1.22~2.90,P<0.05)。结论与非甲状腺癌对照组比较,甲状腺癌病例组MUC1呈高表达,且MUC1高表达与淋巴结转移、TNM分期密切相关。MUC1与甲状腺癌的发生和发展存在相关性,有望成为甲状腺癌分子研究领域的一项新靶标。
文摘Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.
文摘目的·探究黏蛋白1(mucin 1,MUC1)调控肿瘤细胞增殖、迁移和干性维持的功能位点。方法·通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析寻找MUC1基因在不同癌症中的突变特征,对不同MUC1突变位点进行分析及定位,并按突变出现频率排序;通过Western blotting筛选出突变频率较高且蛋白稳定表达的MUC1突变体,利用乳腺癌细胞株BT549敲除MUC1细胞系和乳腺非转化细胞株MCF-10A,应用慢病毒表达系统构建MUC1野生型(MUC1-WT)和突变体稳定表达的细胞系。采用免疫荧光法检测不同MUC1突变体的细胞定位。以MUC1-WT为阳性对照、MUC1-AQA功能丧失突变体为阴性对照,对不同突变细胞的肿瘤生物学功能进行分析:通过细胞计数试剂盒-8(cell counting kit-8,CCK-8)及克隆形成实验检测细胞增殖能力;通过划痕实验及Transwell实验检测细胞迁移能力;通过成球实验检测细胞干性。使用PyMOL软件分析MUC1突变体结构定位并通过蛋白质对接软件(ZDOCK Server)进行分子对接分析。结果·在TCGA数据库中得到102个位于MUC1编码区的突变,其中P418S、S251R、V359I、N271S、N465H 5个错义突变出现频率较高且位于非数目可变串联重复序列(non-variable number of tandem repeats,non-VNTR)区域。进一步检测发现MUC1-S251R、N271S、V359I突变体可稳定表达;细胞定位分析发现这3个突变体主要分布于细胞质,同时细胞核也有一定的分布,核质比与野生型未见明显差异。表达不同MUC1突变体细胞的肿瘤生物学功能分析发现:①MUC1-WT高表达显著增强BT549和MCF-10A细胞的增殖能力;与MUC1-WT细胞相比,MUC1-AQA、S251R、N271S突变体细胞增殖能力下降,但MUC1-V359I突变体细胞与MUC1-WT细胞具有相似的增殖能力。②MUC1-WT高表达细胞的迁移能力显著增强,而MUC1-AQA细胞迁移能力减弱。在BT549细胞中,MUC1-S251R与MUC1-V359I突变体细胞迁移能力与MUC1-WT细胞相似,但MUC1-N271S细胞的迁移能力较MUC1-WT细胞降低。在MCF-10A细胞中,MUC1-N271S与MUC1-V359I细胞的迁移能力接近MUC1-WT细胞;但MUC1-S251R细胞较MUC1-WT细胞迁移能力显著下降。③MUC1-WT高表达显著增强2种细胞的干性,而MUC1-AQA细胞干性丧失;MUC1-N271S、V359I与MUC1-WT具有相似的维持细胞干性的能力,而MUC1-S251R使细胞干性减弱。PyMOL软件分析结果显示,MUC1-N271S及V359I位于海胆精子蛋白-肠激酶-聚集蛋白(sperm protein-enterokinase-agarin,SEA)区域及附近,分别处于loop区及β-折叠处;分子对接结果显示,MUC1-WT及V359I与表皮生长因子受体(epidermal growth factor receptor,EGFR)胞外域形成复合物的稳定性强于MUC1-N271S和S251R,其稳定性排序为V359I>WT>N271S>S251R。结论·MUC1突变体对肿瘤细胞的生物学功能具有不同影响,其对增殖能力影响可能与EGFR信号通路相关。MUC1-V359I与MUC1-WT相似,并未影响MUC1对肿瘤细胞增殖、迁移及干性维持的作用;而MUC1-S251、N271位点可能参与细胞增殖和迁移的信号通路调控且MUC1-S251位点对维持细胞干性较为重要。
基金This study was supported by grants from the Shanghai Scientific Technology Council (No.034119861)a:Contributed equally to the paper
文摘Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.
