Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and im...Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.展开更多
Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet...Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor prognosis.However,the mechanism of metastasis remains poorly underst...BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor prognosis.However,the mechanism of metastasis remains poorly understood.AIM To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment.METHODS The candidate molecule lecithin-cholesterol acyltransferase(LCAT)was screened by gene microarray and bioinformatics analysis.The expression levels of LCAT in clinical cohort samples was detected by quantitative realtime polymerase chain reaction and western blotting.The proliferation,migration,invasion and tumor-forming ability were measured by Cell Counting Kit-8,Transwell cell migration,invasion,and clonal formation assays,respectively.Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression.The immunohistochemistry for Ki67,E-cadherin,N-cadherin,matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC.Gene set enrichment analysis(GSEA)on various gene signatures were analyzed with GSEA version 3.0.Three machine-learning algorithms(random forest,support vector machine,and logistic regression)were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases.RESULTS LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues.LCAT was significantly downregulated in HCC tissues,which is correlated with recurrence,metastasis and poor outcome of HCC patients.Functional analysis indicated that LCAT inhibited HCC cell proliferation,migration and invasion both in vitro and in vivo.Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis(HCC size≤3 cm vs 3-9 cm,P<0.001;3-9 cm vs>9 cm,P<0.01;metastatic-free HCC vs extrahepatic metastatic HCC,P<0.05).LCAT suppressed the growth,migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling.Our results indicated that the logistic regression model based on LCAT,TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients.CONCLUSION LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling.LCAT is a prognostic marker and potential therapeutic target for HCC.展开更多
Myeloid-derived suppressor cells(MDSCs)are bone marrow(BM)-derived immunosuppressive cells in the tumor microenvironment,but the mechanism of MDSC mobilization from the BM remains unclear.We investigated how BM stroma...Myeloid-derived suppressor cells(MDSCs)are bone marrow(BM)-derived immunosuppressive cells in the tumor microenvironment,but the mechanism of MDSC mobilization from the BM remains unclear.We investigated how BM stromal cell activation by PTH1R contributes to MDSC mobilization.PTH1R activation by parathyroid hormone(PTH)or PTH-related peptide(PTHrP),a tumor-derived counterpart,mobilized monocytic(M-)MDSCs from murine BM without increasing immunosuppressive activity.In vitro cell-binding assays demonstrated thatα4β1 integrin and vascular cell adhesion molecule(VCAM)-1,expressed on M-MDSCs and osteoblasts,respectively,are key to M-MDSC binding to osteoblasts.Upon PTH1R activation,osteoblasts express VEGF-A and IL6,leading to Src family kinase phosphorylation in M-MDSCs.Src inhibitors suppressed PTHrP-induced MDSC mobilization,and Src activation in M-MDSCs upregulated two proteases,ADAM-17 and MMP7,leading to VCAM1 shedding and subsequent disruption of M-MDSC tethering to osteoblasts.Collectively,our data provide the molecular mechanism of M-MDSC mobilization in the bones of tumor hosts.展开更多
This study was designed to investigate the roles of RASAL2 in cervical cancer(CC).Methods:Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and Ju...This study was designed to investigate the roles of RASAL2 in cervical cancer(CC).Methods:Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and June 2014.Real-time polymerase chain reaction and western blotting were performed to analyze the expression of RASAL2 mRNA and protein in these tissues,CC cell lines,and normal cervical cells.Over-expression and silencing of RASAL2 were induced after transfection,and the migration,invasion,and proliferation of the CC cell lines were examined.Results:RASAL2 mRNA and protein expressions were significantly down-regulated in CC tissues and cell lines than in adjacent tissues and normal cervical cells,respectively.While low RASAL2 expression correlated with advanced stage and metastasis of CC,its over-expression significantly inhibited proliferation and metastasis of CC cells and induced apoptosis.Under in vitro conditions,silencing of RASAL2 expression could significantly increase the proliferation,invasion,and migration of CC cells.Conclusion:RASAL2 functioned as a tumor suppressor in CC,and was down-regulated in CC tissue samples and cell lines.展开更多
BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesi...BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesion and migration,thereby enhancing tumor proliferation and metastasis.However,the correlation between RSU1 and gastrointestinal cancers(GICs),as well as its prognostic role related to tumor-infiltrating immune cells(TIICs)remains unclear.AIM To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.METHODS Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis(GEPIA)dataset.The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter.Then,RSU1-correlated genes were screened and functionally characterized via enrichment analysis.The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource(TIMER).In addition,the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.RESULTS High RSU1 expression was associated with poor overall survival of gastric cancer patients,exhibiting a hazard ratio(HR)=1.36,first progression HR=1.53,and post progression survival HR=1.6.Specifically,high RSU1 Levels were associated with prognosis of gastric cancer in females,T4 and N3 stages,and Her-2-negative subtypes.Regarding immune-infiltrating cells,RSU1 expression level was positively correlated with infiltration of CD4+T cells,macrophages,neutrophils,and dendritic cells(DCs)in colorectal adenocarcinoma and stomach adenocarcinoma.RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage,DCs and T cell exhaustion in GICs.CONCLUSION In gastrointestinal cancers,RSU1 is increased in tumor tissues,and predicts poor survival of patients.Increased RSU1 may be involved in promoting macrophage polarization,DC infiltration,and T cell exhaustion,inducing tumor immune escape and the development of tumors in GICs.We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs,as well as a potential therapeutic target for precision treatment through improving the immune response.展开更多
目的探究强直性脊柱炎(ankylosing spondylitis,AS)模型小鼠和临床患者外周血单个核细胞(peripheralblood mononuclear cell,PBMC)中微小RNA-142-5p(miR-142-5p),细胞因子信号转导抑制因子1(suppressor ofcytokine signaling 1,SOCS1)m...目的探究强直性脊柱炎(ankylosing spondylitis,AS)模型小鼠和临床患者外周血单个核细胞(peripheralblood mononuclear cell,PBMC)中微小RNA-142-5p(miR-142-5p),细胞因子信号转导抑制因子1(suppressor ofcytokine signaling 1,SOCS1)mRNA表达及其对免疫功能的影响。方法通过实时荧光定量(quantitative real timePCR,qRT-PCR)检测2022年1月~2023年3月商丘市第一人民医院收治的30例确诊的AS患者(患者组)和30例健康体检者(健康组)的PBMC中miR-142-5p和SOCS1 mRNA水平。采用牛蛋白聚糖联合完全弗氏佐剂诱导AS小鼠模型,然后将小鼠分为对照组、模型组、阴性组和拮抗剂组。对照组和模型组小鼠尾静脉注射生理盐水,阴性组和拮抗剂组小鼠分别尾静脉注射NC-antagomir和miR-142-5p-antagomir。治疗2周后,分别评估各组小鼠的关节炎症状评分。通过苏木精伊红(hematoxylin eosin,HE)染色评价踝关节形态。采用ELISA法检测小鼠血清中Th1细胞因子干扰素γ(IFN-γ)、Th2细胞因子白细胞介素-4(IL-4)、Th17细胞因子白细胞介素-17(IL-17)和Treg细胞因子叉头盒蛋白P3(FOXP3)的表达水平。通过qRT-PCR和Western blot检测PBMC和踝关节组织中miR-142-5p,SOCS1,IFN-γ,IL-4,IL-17和FOXP3的mRNA和蛋白表达水平。结果与健康组比较,患者组PBMC中miR-142-5p水平升高(3.03±0.99 vs1.00±0.21),SOCS1 mRNA水平降低(0.41±0.09 vs 1.00±0.18),差异具有统计学意义(t=10.997,15.956,均P<0.001)。与对照组比较,模型组小鼠踝关节组织中miR-142-5p水平(4.00±0.52 vs 1.00±0.04)升高,IFN-γ和IL-17的mRNA和蛋白水平均升高,SOCS1,IL-4和FOXP3的mRNA和蛋白水平均降低,差异具有统计学意义(t=23.356,31.420,48.056,47.224,38.035,29.007,54.183,28.123,55.155,26.758,45.346,均P<0.05);关节炎症状评分升高(7.83±0.94 vs 0.00±0.00,t=22.212,P<0.05),踝关节结构破坏明显;血清中IFN-γ,IL-17水平以及IFN-γ/IL-4比值(0.81±0.08 vs 2.08±0.33)和IL-17/FOXP3比值(0.41±0.03 vs 1.27±0.10)均升高,差异具有统计学意义(t=15.382,35.779,15.412,35.130,均P<0.05)。与阴性组比较,拮抗剂组小鼠踝关节组织中miR-142-5p水平(1.47±0.10 vs 3.89±0.33)降低,IFN-γ和IL-17的mRNA和蛋白水平均降低,SOCS1,IL-4和FOXP3的mRNA和蛋白水平均升高,差异具有统计学意义(t=18.846,22.969,43.454,32.617,23.259,20.881,41.832,11.994,32.977,15.190,35.834,均P<0.05);关节炎症状评分降低(7.42±1.24 vs 2.75±0.75,t=13.233,P<0.05),踝关节形态明显改善;血清中IFN-γ,IL-17水平以及IFN-γ/IL-4比值(1.22±0.11 vs 1.91±0.19)和IL-17/FOXP3比值(0.69±0.05vs 1.23±0.12)均降低,差异具有统计学意义(t=8.688,22.972,8.377,22.007,均P<0.05)。结论miR-142-5p在AS中高表达,使用拮抗剂下调miR-142-5p可能通过上调SOCS1进而降低Th1/Th2和Th17/Treg比值,从而改善AS小鼠的免疫平衡并抑制AS的进展。展开更多
基金Supported by National Natural Science Foundation of China,No.82320108022,No.82322076 and No.82104466.
文摘Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.
基金supported by the Taipei Tzu Chi Hospital through grants from the Buddhist Tzu Chi Medical Foundation under the Numbers TCRD-TPE-111-23(2/3)and TCRD-TPE-113-20,Taipei,Taiwan.
文摘Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.
基金Supported by the National Natural Science Foundation of China,No.92159305National Key R&D Program of China,No.2023YFC2308104.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor prognosis.However,the mechanism of metastasis remains poorly understood.AIM To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment.METHODS The candidate molecule lecithin-cholesterol acyltransferase(LCAT)was screened by gene microarray and bioinformatics analysis.The expression levels of LCAT in clinical cohort samples was detected by quantitative realtime polymerase chain reaction and western blotting.The proliferation,migration,invasion and tumor-forming ability were measured by Cell Counting Kit-8,Transwell cell migration,invasion,and clonal formation assays,respectively.Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression.The immunohistochemistry for Ki67,E-cadherin,N-cadherin,matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC.Gene set enrichment analysis(GSEA)on various gene signatures were analyzed with GSEA version 3.0.Three machine-learning algorithms(random forest,support vector machine,and logistic regression)were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases.RESULTS LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues.LCAT was significantly downregulated in HCC tissues,which is correlated with recurrence,metastasis and poor outcome of HCC patients.Functional analysis indicated that LCAT inhibited HCC cell proliferation,migration and invasion both in vitro and in vivo.Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis(HCC size≤3 cm vs 3-9 cm,P<0.001;3-9 cm vs>9 cm,P<0.01;metastatic-free HCC vs extrahepatic metastatic HCC,P<0.05).LCAT suppressed the growth,migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling.Our results indicated that the logistic regression model based on LCAT,TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients.CONCLUSION LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling.LCAT is a prognostic marker and potential therapeutic target for HCC.
基金in part supported by the National R&D Program for Cancer Control,the Ministry of Health and Welfare,the Republic of Korea(HA17C0040 to SIP)the National Research Foundation of the Republic of Korea(2018R1D1A1B07050329 and2020R1A2C1012966 to SIP,and 2020R1F1A1076996 to SPJ)the Korea University Research Grants(SIP)。
文摘Myeloid-derived suppressor cells(MDSCs)are bone marrow(BM)-derived immunosuppressive cells in the tumor microenvironment,but the mechanism of MDSC mobilization from the BM remains unclear.We investigated how BM stromal cell activation by PTH1R contributes to MDSC mobilization.PTH1R activation by parathyroid hormone(PTH)or PTH-related peptide(PTHrP),a tumor-derived counterpart,mobilized monocytic(M-)MDSCs from murine BM without increasing immunosuppressive activity.In vitro cell-binding assays demonstrated thatα4β1 integrin and vascular cell adhesion molecule(VCAM)-1,expressed on M-MDSCs and osteoblasts,respectively,are key to M-MDSC binding to osteoblasts.Upon PTH1R activation,osteoblasts express VEGF-A and IL6,leading to Src family kinase phosphorylation in M-MDSCs.Src inhibitors suppressed PTHrP-induced MDSC mobilization,and Src activation in M-MDSCs upregulated two proteases,ADAM-17 and MMP7,leading to VCAM1 shedding and subsequent disruption of M-MDSC tethering to osteoblasts.Collectively,our data provide the molecular mechanism of M-MDSC mobilization in the bones of tumor hosts.
基金supported by the National Natural Science Foundation of China(Grant No.81572559)the Shandong Key Research and Development Plan(Grant No.2017CXGC1210).
文摘This study was designed to investigate the roles of RASAL2 in cervical cancer(CC).Methods:Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and June 2014.Real-time polymerase chain reaction and western blotting were performed to analyze the expression of RASAL2 mRNA and protein in these tissues,CC cell lines,and normal cervical cells.Over-expression and silencing of RASAL2 were induced after transfection,and the migration,invasion,and proliferation of the CC cell lines were examined.Results:RASAL2 mRNA and protein expressions were significantly down-regulated in CC tissues and cell lines than in adjacent tissues and normal cervical cells,respectively.While low RASAL2 expression correlated with advanced stage and metastasis of CC,its over-expression significantly inhibited proliferation and metastasis of CC cells and induced apoptosis.Under in vitro conditions,silencing of RASAL2 expression could significantly increase the proliferation,invasion,and migration of CC cells.Conclusion:RASAL2 functioned as a tumor suppressor in CC,and was down-regulated in CC tissue samples and cell lines.
基金Supported by the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2023A1515012762+2 种基金and 2021A1515012180Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesion and migration,thereby enhancing tumor proliferation and metastasis.However,the correlation between RSU1 and gastrointestinal cancers(GICs),as well as its prognostic role related to tumor-infiltrating immune cells(TIICs)remains unclear.AIM To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.METHODS Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis(GEPIA)dataset.The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter.Then,RSU1-correlated genes were screened and functionally characterized via enrichment analysis.The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource(TIMER).In addition,the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.RESULTS High RSU1 expression was associated with poor overall survival of gastric cancer patients,exhibiting a hazard ratio(HR)=1.36,first progression HR=1.53,and post progression survival HR=1.6.Specifically,high RSU1 Levels were associated with prognosis of gastric cancer in females,T4 and N3 stages,and Her-2-negative subtypes.Regarding immune-infiltrating cells,RSU1 expression level was positively correlated with infiltration of CD4+T cells,macrophages,neutrophils,and dendritic cells(DCs)in colorectal adenocarcinoma and stomach adenocarcinoma.RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage,DCs and T cell exhaustion in GICs.CONCLUSION In gastrointestinal cancers,RSU1 is increased in tumor tissues,and predicts poor survival of patients.Increased RSU1 may be involved in promoting macrophage polarization,DC infiltration,and T cell exhaustion,inducing tumor immune escape and the development of tumors in GICs.We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs,as well as a potential therapeutic target for precision treatment through improving the immune response.
文摘目的探究强直性脊柱炎(ankylosing spondylitis,AS)模型小鼠和临床患者外周血单个核细胞(peripheralblood mononuclear cell,PBMC)中微小RNA-142-5p(miR-142-5p),细胞因子信号转导抑制因子1(suppressor ofcytokine signaling 1,SOCS1)mRNA表达及其对免疫功能的影响。方法通过实时荧光定量(quantitative real timePCR,qRT-PCR)检测2022年1月~2023年3月商丘市第一人民医院收治的30例确诊的AS患者(患者组)和30例健康体检者(健康组)的PBMC中miR-142-5p和SOCS1 mRNA水平。采用牛蛋白聚糖联合完全弗氏佐剂诱导AS小鼠模型,然后将小鼠分为对照组、模型组、阴性组和拮抗剂组。对照组和模型组小鼠尾静脉注射生理盐水,阴性组和拮抗剂组小鼠分别尾静脉注射NC-antagomir和miR-142-5p-antagomir。治疗2周后,分别评估各组小鼠的关节炎症状评分。通过苏木精伊红(hematoxylin eosin,HE)染色评价踝关节形态。采用ELISA法检测小鼠血清中Th1细胞因子干扰素γ(IFN-γ)、Th2细胞因子白细胞介素-4(IL-4)、Th17细胞因子白细胞介素-17(IL-17)和Treg细胞因子叉头盒蛋白P3(FOXP3)的表达水平。通过qRT-PCR和Western blot检测PBMC和踝关节组织中miR-142-5p,SOCS1,IFN-γ,IL-4,IL-17和FOXP3的mRNA和蛋白表达水平。结果与健康组比较,患者组PBMC中miR-142-5p水平升高(3.03±0.99 vs1.00±0.21),SOCS1 mRNA水平降低(0.41±0.09 vs 1.00±0.18),差异具有统计学意义(t=10.997,15.956,均P<0.001)。与对照组比较,模型组小鼠踝关节组织中miR-142-5p水平(4.00±0.52 vs 1.00±0.04)升高,IFN-γ和IL-17的mRNA和蛋白水平均升高,SOCS1,IL-4和FOXP3的mRNA和蛋白水平均降低,差异具有统计学意义(t=23.356,31.420,48.056,47.224,38.035,29.007,54.183,28.123,55.155,26.758,45.346,均P<0.05);关节炎症状评分升高(7.83±0.94 vs 0.00±0.00,t=22.212,P<0.05),踝关节结构破坏明显;血清中IFN-γ,IL-17水平以及IFN-γ/IL-4比值(0.81±0.08 vs 2.08±0.33)和IL-17/FOXP3比值(0.41±0.03 vs 1.27±0.10)均升高,差异具有统计学意义(t=15.382,35.779,15.412,35.130,均P<0.05)。与阴性组比较,拮抗剂组小鼠踝关节组织中miR-142-5p水平(1.47±0.10 vs 3.89±0.33)降低,IFN-γ和IL-17的mRNA和蛋白水平均降低,SOCS1,IL-4和FOXP3的mRNA和蛋白水平均升高,差异具有统计学意义(t=18.846,22.969,43.454,32.617,23.259,20.881,41.832,11.994,32.977,15.190,35.834,均P<0.05);关节炎症状评分降低(7.42±1.24 vs 2.75±0.75,t=13.233,P<0.05),踝关节形态明显改善;血清中IFN-γ,IL-17水平以及IFN-γ/IL-4比值(1.22±0.11 vs 1.91±0.19)和IL-17/FOXP3比值(0.69±0.05vs 1.23±0.12)均降低,差异具有统计学意义(t=8.688,22.972,8.377,22.007,均P<0.05)。结论miR-142-5p在AS中高表达,使用拮抗剂下调miR-142-5p可能通过上调SOCS1进而降低Th1/Th2和Th17/Treg比值,从而改善AS小鼠的免疫平衡并抑制AS的进展。
