目的基于生物信息学分析HMGA2基因在脑胶质瘤中的表达和预后意义,并推断HMGA2对脑胶质瘤发生、发展的生物学功能。方法从中国脑胶质瘤基因组图谱数据库(Chinese Glioma Genome Atlas,CGGA)和癌症基因组图谱(the Cancer Genome Atlas,TC...目的基于生物信息学分析HMGA2基因在脑胶质瘤中的表达和预后意义,并推断HMGA2对脑胶质瘤发生、发展的生物学功能。方法从中国脑胶质瘤基因组图谱数据库(Chinese Glioma Genome Atlas,CGGA)和癌症基因组图谱(the Cancer Genome Atlas,TCGA)中各自获取693例和697例脑胶质瘤的基因表达数据集以及临床信息数据集,对HMGA2的不同表达状态进行研究。采用Kaplan-Meier生存曲线法和Cox分析法分析HMGA2对脑胶质瘤预后的预测价值。通过基因本体论(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析预测HMGA2可能富集的通路。将HMGA2与血管生成相关基因集进行基因集变异分析(gene set variation analysis,GSVA)。结果HMGA2在胶质瘤高级别、异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)野生型、无1p/19q共缺失的组别中高表达。生存分析显示,HMGA2较高表达脑胶质瘤患者的总生存期(overall survival,OS)显著低于HMGA2较低表达的OS(P<0.0001)。在Cox回归分析中,HMGA2表达水平是OS的独立预后因素。GO和KEGG分析显示,HMGA2富集在血管生成、内质网腔、细胞凋亡、肿瘤中的蛋白聚糖、蛋白结合、细胞外基质与受体的相互作用、焦点黏附、PI3KAKT信号通路等。GSVA结果显示HMGA2表达与血管生成呈正相关。结论HMGA2的表达与脑胶质瘤的病理级别和分子标志物密切相关,HMGA2高表达的脑胶质瘤患者预后较差,HMGA2能够影响胶质瘤的发生、发展,有望作为脑胶质瘤患者的预测标志物和治疗靶点。展开更多
目的:探究宫腔粘连(Intrauterine adhesion,IUA)患者子宫内膜组织中高迁移率族蛋白B1(High mobility group box1,HMGB1)、高迁移率族蛋白A2(High mobility group protein A2,HMGA2)和表皮生长因子受体(Epidermal growth factor receptor...目的:探究宫腔粘连(Intrauterine adhesion,IUA)患者子宫内膜组织中高迁移率族蛋白B1(High mobility group box1,HMGB1)、高迁移率族蛋白A2(High mobility group protein A2,HMGA2)和表皮生长因子受体(Epidermal growth factor receptor,EGFR)表达与病情及预后关系。方法:选取2021年8月-2023年8月本院收治的68例IUA患者(IUA组)和60例正常宫腔患者(对照组),采用免疫组化法检测HMGB1、HMGA2和EGFR表达,分析其与病情严重程度及预后不良的关系。结果:IUA组HMGB1阳性表达率低于对照组,HMGA2和EGFR阳性表达率显著升高(P<0.05)。随着病情加重,IUA患者子宫内膜组织中HMGB1阳性表达率依次降低,HMGA2和EGFR阳性表达率依次升高(P<0.05)。单因素分析显示,患者预后不良与流产史、术前月经量、粘连范围、粘连性质、HMGB1、HMGA2及EGFR表达情况有关(P<0.05),与年龄和病程无关(P>0.05)。多因素Logistic回归分析显示,流产史>3次、术前闭经、粘连范围>2/3、粘连性质肌性、HMGB1阴性表达、HMGA2及EGFR阳性表达是患者术后复发的危险因素(P<0.05)。结论:IUA患者子宫内膜组织中HMGB1低表达及HMGA2和EGFR高表达与患者病情程度及预后有关,可作为患者患病程度及不良预后的评估指标。展开更多
Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and do...Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.展开更多
BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in t...BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.展开更多
In the article“Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA”(Oncology Research,2020,Vol.28,No.5,pp....In the article“Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA”(Oncology Research,2020,Vol.28,No.5,pp.483–495.doi:10.3727/096504020X15928179818438),there was an error in the processing of data.To further confirm our observation,we repeated multiple experiments involving in this study,including Flow Cytometry,Transwell Cell Migration and Invasion Assays,Xenograft Tumor Model,and Western Blotting.We have revised the figures to correct these errors.Corrected versions of the Figs.2,4,5,6,and 7 are provided.The corrections do not change any results or conclusion of the article.We apologize for any inconvenience caused.展开更多
背景与目的高迁移率族蛋白A2(High mobility group A2,HMGA2)是与染色体结合的非组蛋白,在许多恶性肿瘤中高表达并与预后有关。本研究探讨HMGA2在非小细胞肺癌(NSCLC)中的表达的临床特征及其意义。方法采用免疫组化SP法检测59例手术切...背景与目的高迁移率族蛋白A2(High mobility group A2,HMGA2)是与染色体结合的非组蛋白,在许多恶性肿瘤中高表达并与预后有关。本研究探讨HMGA2在非小细胞肺癌(NSCLC)中的表达的临床特征及其意义。方法采用免疫组化SP法检测59例手术切除非小细胞肺癌组织,10例非肿瘤组织中HMGA2表达。采用c2检验,Kaplan-Meier生存曲线和Cox回归分析,比较与HMGA2表达相关因素及其对生存期的影响。结果非小细胞肺癌组织中HMGA2表达率78%(46/59),其中肺鳞癌表达率70.4%(19/27),肺腺癌表达率82.1%(23/28),4例腺鳞癌均表达,而10例非肿瘤组织中均不表达。HMGA2表达与TNM分期,淋巴结转移相关(P<0.05)。Cox多因素回归分析显示TNM分期是本组患者独立预后因子。结论HMGA2在非小细胞肺癌中呈过度表达,与TNM分期、淋巴结转移相关。展开更多
文摘目的基于生物信息学分析HMGA2基因在脑胶质瘤中的表达和预后意义,并推断HMGA2对脑胶质瘤发生、发展的生物学功能。方法从中国脑胶质瘤基因组图谱数据库(Chinese Glioma Genome Atlas,CGGA)和癌症基因组图谱(the Cancer Genome Atlas,TCGA)中各自获取693例和697例脑胶质瘤的基因表达数据集以及临床信息数据集,对HMGA2的不同表达状态进行研究。采用Kaplan-Meier生存曲线法和Cox分析法分析HMGA2对脑胶质瘤预后的预测价值。通过基因本体论(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析预测HMGA2可能富集的通路。将HMGA2与血管生成相关基因集进行基因集变异分析(gene set variation analysis,GSVA)。结果HMGA2在胶质瘤高级别、异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)野生型、无1p/19q共缺失的组别中高表达。生存分析显示,HMGA2较高表达脑胶质瘤患者的总生存期(overall survival,OS)显著低于HMGA2较低表达的OS(P<0.0001)。在Cox回归分析中,HMGA2表达水平是OS的独立预后因素。GO和KEGG分析显示,HMGA2富集在血管生成、内质网腔、细胞凋亡、肿瘤中的蛋白聚糖、蛋白结合、细胞外基质与受体的相互作用、焦点黏附、PI3KAKT信号通路等。GSVA结果显示HMGA2表达与血管生成呈正相关。结论HMGA2的表达与脑胶质瘤的病理级别和分子标志物密切相关,HMGA2高表达的脑胶质瘤患者预后较差,HMGA2能够影响胶质瘤的发生、发展,有望作为脑胶质瘤患者的预测标志物和治疗靶点。
文摘目的:探究宫腔粘连(Intrauterine adhesion,IUA)患者子宫内膜组织中高迁移率族蛋白B1(High mobility group box1,HMGB1)、高迁移率族蛋白A2(High mobility group protein A2,HMGA2)和表皮生长因子受体(Epidermal growth factor receptor,EGFR)表达与病情及预后关系。方法:选取2021年8月-2023年8月本院收治的68例IUA患者(IUA组)和60例正常宫腔患者(对照组),采用免疫组化法检测HMGB1、HMGA2和EGFR表达,分析其与病情严重程度及预后不良的关系。结果:IUA组HMGB1阳性表达率低于对照组,HMGA2和EGFR阳性表达率显著升高(P<0.05)。随着病情加重,IUA患者子宫内膜组织中HMGB1阳性表达率依次降低,HMGA2和EGFR阳性表达率依次升高(P<0.05)。单因素分析显示,患者预后不良与流产史、术前月经量、粘连范围、粘连性质、HMGB1、HMGA2及EGFR表达情况有关(P<0.05),与年龄和病程无关(P>0.05)。多因素Logistic回归分析显示,流产史>3次、术前闭经、粘连范围>2/3、粘连性质肌性、HMGB1阴性表达、HMGA2及EGFR阳性表达是患者术后复发的危险因素(P<0.05)。结论:IUA患者子宫内膜组织中HMGB1低表达及HMGA2和EGFR高表达与患者病情程度及预后有关,可作为患者患病程度及不良预后的评估指标。
基金Fujian Provincial Health and Middleaged and Young Backbone Talents Training Project“The role and Mechanism of C53 in mcRPC Treatment of Drug Resistance”(2019-ZQN-77).
文摘Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.
基金Supported by Natural Science Foundation of Anhui Province,No.2108085QH337Research Fund of Anhui Medical University,No.2022xkj156+1 种基金Key Projects of Anhui Provincial Department of Education,No.2023AH053330Anhui Institute of Translational Medicine Research Fund,No.2022zhyx-C88.
文摘BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.
文摘In the article“Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA”(Oncology Research,2020,Vol.28,No.5,pp.483–495.doi:10.3727/096504020X15928179818438),there was an error in the processing of data.To further confirm our observation,we repeated multiple experiments involving in this study,including Flow Cytometry,Transwell Cell Migration and Invasion Assays,Xenograft Tumor Model,and Western Blotting.We have revised the figures to correct these errors.Corrected versions of the Figs.2,4,5,6,and 7 are provided.The corrections do not change any results or conclusion of the article.We apologize for any inconvenience caused.
文摘背景与目的高迁移率族蛋白A2(High mobility group A2,HMGA2)是与染色体结合的非组蛋白,在许多恶性肿瘤中高表达并与预后有关。本研究探讨HMGA2在非小细胞肺癌(NSCLC)中的表达的临床特征及其意义。方法采用免疫组化SP法检测59例手术切除非小细胞肺癌组织,10例非肿瘤组织中HMGA2表达。采用c2检验,Kaplan-Meier生存曲线和Cox回归分析,比较与HMGA2表达相关因素及其对生存期的影响。结果非小细胞肺癌组织中HMGA2表达率78%(46/59),其中肺鳞癌表达率70.4%(19/27),肺腺癌表达率82.1%(23/28),4例腺鳞癌均表达,而10例非肿瘤组织中均不表达。HMGA2表达与TNM分期,淋巴结转移相关(P<0.05)。Cox多因素回归分析显示TNM分期是本组患者独立预后因子。结论HMGA2在非小细胞肺癌中呈过度表达,与TNM分期、淋巴结转移相关。
