Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2024051776
Fan Fang, Cheng Chen
Alzheimer's disease (AD) is the most common form of dementia. Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of AD. In a large case-control study recruiting 208 patients with AD and 205 elderly control subjects, miRNA-let-7d-5p attracted our attention for its downregulated level in patients with AD. However, the biological functions of let-7d-5p in AD pathogenesis have not been investigated. This study emphasized the functions and mechanisms of let-7d-5p in the pathogenesis of AD. Mouse microglial BV2 cells treated with amyloid-β (Aβ)1-42 were used as in vitro AD inflammation models. We reported that let-7d-5p was downregulated in Aβ 1-42-stimulated BV2 cells, and upregulation of let-7d-5p promoted the transversion of microglial cells from Ml phenotype to M2 phenotype. Then, the binding relationship between let-7d-5p and Map3k1 was verified by luciferase reporter assays. Mechanistically, let-7d-5p could target Map3k1 3'UTR to inactivate ERK/p38 MAPK signaling. Therefore, it was suggested that let-7d-5p might be a novel modulator of microglial neuroinflammation and serve as a novel target for diagnosis and treatment of AD.
阿尔茨海默病（AD）是最常见的痴呆症。微RNA（miRNA）的异常调控与阿尔茨海默病的发病机制有关。在一项招募了208名AD患者和205名老年对照受试者的大型病例对照研究中，miRNA-let-7d-5p因其在AD患者中的下调水平而引起了我们的注意。然而，let-7d-5p 在 AD 发病机制中的生物学功能尚未得到研究。本研究强调了let-7d-5p在AD发病机制中的功能和机制。我们用淀粉样蛋白-β（Aβ）1-42处理的小鼠小胶质细胞BV2作为体外AD炎症模型。我们发现，let-7d-5p在Aβ 1-42刺激的BV2细胞中被下调，而let-7d-5p的上调促进了小胶质细胞从Ml表型向M2表型的转化。然后，通过荧光素酶报告实验验证了let-7d-5p与Map3k1的结合关系。从机理上讲，let-7d-5p可以靶向Map3k1的3'UTR，使ERK/p38 MAPK信号失活。因此，let-7d-5p可能是一种新型的小胶质细胞神经炎症调节剂，并可作为诊断和治疗AD的新靶点。
{"title":"MiRNA let-7d-5p Alleviates Inflammatory Responses by Targeting Map3k1 and Inactivating ERK/p38 MAPK Signaling in Microglia","authors":"Fan Fang, Cheng Chen","doi":"10.1615/critrevimmunol.2024051776","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051776","url":null,"abstract":"Alzheimer's disease (AD) is the most common form of dementia. Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of AD. In a large case-control study recruiting 208 patients with AD and 205 elderly control subjects, miRNA-let-7d-5p attracted our attention for its downregulated level in patients with AD. However, the biological functions of let-7d-5p in AD pathogenesis have not been investigated. This study emphasized the functions and mechanisms of let-7d-5p in the pathogenesis of AD. Mouse microglial BV2 cells treated with amyloid-β (Aβ)<sub>1-42</sub> were used as <i>in vitro</i> AD inflammation models. We reported that let-7d-5p was downregulated in Aβ <sub>1-42</sub>-stimulated BV2 cells, and upregulation of let-7d-5p promoted the transversion of microglial cells from Ml phenotype to M2 phenotype. Then, the binding relationship between let-7d-5p and Map3k1 was verified by luciferase reporter assays. Mechanistically, let-7d-5p could target Map3k1 3'UTR to inactivate ERK/p38 MAPK signaling. Therefore, it was suggested that let-7d-5p might be a novel modulator of microglial neuroinflammation and serve as a novel target for diagnosis and treatment of AD.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"29 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140313099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2023051066
Baoshan Ning, Yine Mei
Laminin subunit alpha 3 (LAMA3) is a cancer regulator. However, its effects and regulatory pathways in oral squamous cell carcinoma (OSCC) progression remain unknown. This research aimed to determine the influence of LAMA3 regulation via methyltransferase-like 3 (METTL3) on OSCC progression. Using quantitative real-time polymerase chain reaction and bioinformatics analysis, the expression levels of LAMA3 and METTL3 in OSCC tissues were examined. The functional roles of LAMA3 and METTL3 were analyzed using cell functional experiments. Using methylated RNA immunoprecipitation and mRNA stability assays, LAMA3 and METTL3 regulation was investigated. In OSCC tissues, LAMA3 was upregulated. LAMA3 inhibition hampered OSCC cell proliferation, invasion, and migration while its overexpression facilitated OSCC cell progression. METTL3 serves as a crucial upstream regulator of LAMA3 in OSCC and upregulates LAMA3 expression via an m6A-dependent mechanism. The low METTL3 expression partially restored the enhanced malignant phenotype induced by LAMA3 overexpression. Our findings indicate that METTL3 and LAMA3 act as pro-oncogenic factors in OSCC, with METTL3 promoting OSCC malignancy via m6A modification-dependent stabilization of LAMA3 transcripts, representing a novel regulatory mechanism in OSCC.
{"title":"LAMA3 Promotes Tumorigenesis of Oral Squamous Cell Carcinoma by METTL3-Mediated N6-Methyladenosine Modification","authors":"Baoshan Ning, Yine Mei","doi":"10.1615/critrevimmunol.2023051066","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051066","url":null,"abstract":"Laminin subunit alpha 3 (LAMA3) is a cancer regulator. However, its effects and regulatory pathways in oral squamous cell carcinoma (OSCC) progression remain unknown. This research aimed to determine the influence of LAMA3 regulation via methyltransferase-like 3 (METTL3) on OSCC progression. Using quantitative real-time polymerase chain reaction and bioinformatics analysis, the expression levels of LAMA3 and METTL3 in OSCC tissues were examined. The functional roles of LAMA3 and METTL3 were analyzed using cell functional experiments. Using methylated RNA immunoprecipitation and mRNA stability assays, LAMA3 and METTL3 regulation was investigated. In OSCC tissues, LAMA3 was upregulated. LAMA3 inhibition hampered OSCC cell proliferation, invasion, and migration while its overexpression facilitated OSCC cell progression. METTL3 serves as a crucial upstream regulator of LAMA3 in OSCC and upregulates LAMA3 expression via an m6A-dependent mechanism. The low METTL3 expression partially restored the enhanced malignant phenotype induced by LAMA3 overexpression. Our findings indicate that METTL3 and LAMA3 act as pro-oncogenic factors in OSCC, with METTL3 promoting OSCC malignancy via m6A modification-dependent stabilization of LAMA3 transcripts, representing a novel regulatory mechanism in OSCC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"19 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138537043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-tuberculous mycobacteria (NTM) infection is common in bronchiectasis, with rising incidence globally. However, investigation into NTM in bronchiectasis patients in China remains relatively limited. This work aimed to identify and understand the features of NTM in bronchiectasis patient in Fuzhou district of China. The pulmonary samples were collected from 281 bronchiectasis patients with suspected NTM infection in Fuzhou, 2018-2022. MPB64 antigen detection was employed for the preliminary evaluation of NTM. Further NTM identification was realized using gene chip and gene sequencing. Among 281 patients, 172 (61.21%) patients were NTM-positive (58.72%) according to MPB64 antigen detection, with females (58.72%) outnumbering males (41.28%) and the highest prevalence in the age group of 46-65 years. In total, 47 NTM single infections and 3 mixed infections (1 Mycobacterium tuberculosis complex-M. intracellulare, 1 M. avium-M. intracellulare, and 1 M. abscessus-M. intracellulare) were identified through multicolor melting curve analysis (MMCA), which was compared with gene sequencing results. Both methods suggested Mycobacterium (M.) intracellulare, M. abscessus, and M. avium as the primary NTM species affecting bronchiectasis patients. M. intracellulare and M. abscessus were more frequent in females than males with the highest prevalence in the age group of 46-65 years according to MMCA. This research provides novel insights into the epidemiological and clinical features of NTM in bronchiectasis patients in Southeastern China. Significantly, M. intracellulare, M. abscessus, and M. avium were identified as the major NTM species, contributing to a better understanding and management of bronchiectasis accompanied by NTM infection.
{"title":"Employing Multicolor Melting Curve Analysis to Rapidly Identify Non-Tuberculous Mycobacteria in Patients with Bronchiectasis: A Study from a Pulmonary Hospital in the Fuzhou District of China, 2018−2022","authors":"Mintao Zheng, Xinchao Chen, Qiaoqian Chen, Xiaohong Chen, Mingxiang Huang","doi":"10.1615/critrevimmunol.2024052213","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052213","url":null,"abstract":"Non-tuberculous mycobacteria (NTM) infection is common in bronchiectasis, with rising incidence globally. However, investigation into NTM in bronchiectasis patients in China remains relatively limited. This work aimed to identify and understand the features of NTM in bronchiectasis patient in Fuzhou district of China. The pulmonary samples were collected from 281 bronchiectasis patients with suspected NTM infection in Fuzhou, 2018-2022. MPB64 antigen detection was employed for the preliminary evaluation of NTM. Further NTM identification was realized using gene chip and gene sequencing. Among 281 patients, 172 (61.21%) patients were NTM-positive (58.72%) according to MPB64 antigen detection, with females (58.72%) outnumbering males (41.28%) and the highest prevalence in the age group of 46-65 years. In total, 47 NTM single infections and 3 mixed infections (1 <i>Mycobacterium tuberculosis complex-M. intracellulare</i>, 1 <i>M. avium-M. intracellulare</i>, and 1 <i>M. abscessus-M. intracellulare</i>) were identified through multicolor melting curve analysis (MMCA), which was compared with gene sequencing results. Both methods suggested <i>Mycobacterium (M.) intracellulare, M. abscessus</i>, and <i>M. avium</i> as the primary NTM species affecting bronchiectasis patients. <i>M. intracellulare</i> and <i>M. abscessus </i>were more frequent in females than males with the highest prevalence in the age group of 46-65 years according to MMCA. This research provides novel insights into the epidemiological and clinical features of NTM in bronchiectasis patients in Southeastern China. Significantly, <i>M. intracellulare, M. abscessus,</i> and <i>M. avium</i> were identified as the major NTM species, contributing to a better understanding and management of bronchiectasis accompanied by NTM infection.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"52 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2023051250
Bin Huang, Chang Xin, Huanjun Yan, Zhewei Yu
This study aimed to construct a blood diagnostic model for pancreatic cancer (PC) using miRNA signatures by a combination of machine learning and biological experimental verification. Gene expression profiles of patients with PC and transcriptome normalization data were obtained from the Gene Expression Omnibus (GEO) database. Using random forest algorithm, lasso regression algorithm, and multivariate cox regression analyses, the classifier of differentially expressed miRNAs was identified based on algorithms and functional properties. Next, the ROC curve analysis was used to evaluate the predictive performance of the diagnostic model. Finally, we analyzed the expression of two specific miRNAs in Capan-1, PANC-1, and MIA PaCa-2 pancreatic cells using qRT-PCR. Integrated microarray analysis revealed that 33 common miRNAs exhibited significant differences in expression profiles between tumor and normal groups (P value < 0.05 and |logFC| > 0.3). Pathway analysis showed that differentially expressed miRNAs were related to P00059 p53 pathway, hsa04062 chemokine signaling pathway, and cancer-related pathways including PC. In ENCORI database, the hsa-miR-4486 and hsa-miR-6075 were identified by random forest algorithm and lasso regression algorithm and introduced as major miRNA markers in PC diagnosis. Further, the receiver operating characteristic curve analysis achieved the area under curve score > 80%, showing good sensitivity and specificity of the two-miRNA signature model in PC diagnosis. Additionally, hsa-miR-4486 and hsa-miR-6075 genes expressions in three pancreatic cells were all up-regulated by qRT-PCR. In summary, these findings suggest that the two miRNAs, hsa-miR-4486 and hsa-miR-6075, could serve as valuable prognostic markers for PC.
{"title":"A Machine Learning Method for a Blood Diagnostic Model of Pancreatic Cancer Based on microRNA Signatures","authors":"Bin Huang, Chang Xin, Huanjun Yan, Zhewei Yu","doi":"10.1615/critrevimmunol.2023051250","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051250","url":null,"abstract":"This study aimed to construct a blood diagnostic model for pancreatic cancer (PC) using miRNA signatures by a combination of machine learning and biological experimental verification. Gene expression profiles of patients with PC and transcriptome normalization data were obtained from the Gene Expression Omnibus (GEO) database. Using random forest algorithm, lasso regression algorithm, and multivariate cox regression analyses, the classifier of differentially expressed miRNAs was identified based on algorithms and functional properties. Next, the ROC curve analysis was used to evaluate the predictive performance of the diagnostic model. Finally, we analyzed the expression of two specific miRNAs in Capan-1, PANC-1, and MIA PaCa-2 pancreatic cells using qRT-PCR. Integrated microarray analysis revealed that 33 common miRNAs exhibited significant differences in expression profiles between tumor and normal groups (<i>P</i> value < 0.05 and |logFC| > 0.3). Pathway analysis showed that differentially expressed miRNAs were related to P00059 p53 pathway, hsa04062 chemokine signaling pathway, and cancer-related pathways including PC. In ENCORI database, the hsa-miR-4486 and hsa-miR-6075 were identified by random forest algorithm and lasso regression algorithm and introduced as major miRNA markers in PC diagnosis. Further, the receiver operating characteristic curve analysis achieved the area under curve score > 80%, showing good sensitivity and specificity of the two-miRNA signature model in PC diagnosis. Additionally, hsa-miR-4486 and hsa-miR-6075 genes expressions in three pancreatic cells were all up-regulated by qRT-PCR. In summary, these findings suggest that the two miRNAs, hsa-miR-4486 and hsa-miR-6075, could serve as valuable prognostic markers for PC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"35 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2024051136
Fei Li, Ying-pei Ling, Pan Wang, Shi-cheng Gu, Hao Jiang, Jie Zhu
Objective: This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms. Methods: We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay. Results: Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells. Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.
研究目的本研究旨在阐明microRNA-503（miR-503）在胰腺癌（PC）进展中的作用及其潜在调控机制：方法：我们从 UCSC Xena 数据库中获取了 miR-503-3p 和 miR-503-5p 的表达数据以及 PC 和正常样本的生存时间。我们用t检验比较了PC样本和正常样本中miR-503-3p和miR-503-5p的表达，并通过Kaplan-Meier生存分析评估了它们的预后意义。我们通过定量 PCR 检测了 miR-503-5p 在 PC 细胞中的表达。随后，我们在 PC 细胞中过表达了 miR-503-5p，并通过 CCK8 检测法、流式细胞术和 Transwell 检测法分别检测了细胞活力、凋亡和迁移。利用 miRTarBase 鉴定了潜在的功能靶点，并通过双荧光素酶报告实验进行了验证：结果：研究发现，miR-503-3p和miR-503-5p在PC中的表达均出现下调；然而，根据公开数据，只有miR-503-5p与癌症预后有关。体外实验表明，miR-503-5p的过表达会大幅降低细胞活力、诱导细胞凋亡、导致G0/G1停滞和抑制细胞迁移。研究发现，miR-503-5p以细胞周期蛋白E2（CCNE2）为靶标，而CCNE2的过表达可抵消miR-503-5p对PC细胞的影响：结论：miR-503-5p的下调通过靶向CCNE2促进PC的进展。结论：miR-503-5p的下调通过靶向CCNE2而促进PC的进展，检测miR-503-5p的表达可为PC的预防和预后评估提供有价值的见解。
{"title":"Downregulation of miR-503-5p promotes the development of pancreatic cancer via targeting cyclin E2","authors":"Fei Li, Ying-pei Ling, Pan Wang, Shi-cheng Gu, Hao Jiang, Jie Zhu","doi":"10.1615/critrevimmunol.2024051136","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051136","url":null,"abstract":"Objective: This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms.\u0000Methods: We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay.\u0000Results: Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells.\u0000Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139461577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2023052095
Cheng He, Yimei Lin, Feng Qiu, Qingxin Zeng
Backgroud: Colorectal cancer is the third most common malignant tumor, with highly invasive and metastatic potential in the later stage. This study investigated the role of PKN2 overexpression and M2-polarized macrophages in dictating the malignant phenotype of colorectal cancer cells. Methods: HCT116 colorectal cancer cell line with PKN2 overexpression was generated to investigate the functional role of PKN2. THP-1 cells were polarized into M2-like macrophages, and the co-culture system of THP-1/M2 cells and HCT116 cells was established to examine the impacts of M2-polairzed macrophages on the malignant phenotype of colorectal cancer cells. Results: PKN2 overexpression promoted cell proliferation, migration and invasion in HCT116 colorectal cancer cells, and reduced spontaneous cell death in the cell culture. Besides, the presence of M2-polarized THP-1 cells significantly enhanced the aggressive phenotype of HCT116 cells. Both PKN2 overexpression and M2-polarized THP-1 cells increased the expression of NF-κB p65 in HCT116 cells, indicating that enhanced NF-κB signaling may contribute to the augmented aggressiveness of HCT116 cells. Conclusion: These findings suggest PKN2 as an oncogenic factor in colorectal cancer and that M2-polarized THP-1 cells may promote the progression of colorectal cancer by activating NF-κB signaling.
{"title":"Increased PKN2 and M2-polarized macrophages promote HCT116 cell invasion","authors":"Cheng He, Yimei Lin, Feng Qiu, Qingxin Zeng","doi":"10.1615/critrevimmunol.2023052095","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023052095","url":null,"abstract":"Backgroud: Colorectal cancer is the third most common malignant tumor, with highly invasive and metastatic potential in the later stage. This study investigated the role of PKN2 overexpression and M2-polarized macrophages in dictating the malignant phenotype of colorectal cancer cells.\u0000Methods: HCT116 colorectal cancer cell line with PKN2 overexpression was generated to investigate the functional role of PKN2. THP-1 cells were polarized into M2-like macrophages, and the co-culture system of THP-1/M2 cells and HCT116 cells was established to examine the impacts of M2-polairzed macrophages on the malignant phenotype of colorectal cancer cells.\u0000Results: PKN2 overexpression promoted cell proliferation, migration and invasion in HCT116 colorectal cancer cells, and reduced spontaneous cell death in the cell culture. Besides, the presence of M2-polarized THP-1 cells significantly enhanced the aggressive phenotype of HCT116 cells. Both PKN2 overexpression and M2-polarized THP-1 cells increased the expression of NF-κB p65 in HCT116 cells, indicating that enhanced NF-κB signaling may contribute to the augmented aggressiveness of HCT116 cells.\u0000Conclusion: These findings suggest PKN2 as an oncogenic factor in colorectal cancer and that M2-polarized THP-1 cells may promote the progression of colorectal cancer by activating NF-κB signaling.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"21 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2024052391
Jian Shen, Minzhe Li
Gastric cancer (GC) is highly heterogeneous and influenced by aging-related factors. This study aimed to improve individualized prognostic assessment of GC by identifying aging-related genes and subtypes. Immune scores of GC samples from GEO and TCGA databases were calculated using ESTIMATE and scored as high immune (IS_high) and low immune (IS_low). ssGSEA was used to analyze immune cell infiltration. Univariate Cox regression was employed to identify prognosis-related genes. LASSO regression analysis was used to construct a prognostic model. GSVA enrichment analysis was applied to determine pathways. CCK-8, wound healing, and Transwell assays tested the proliferation, migration, and invasion of the GC cell line (AGS). Cell cycle and aging were examined using flow cytometry, β-galactosidase staining, and Western blotting. Two aging-related GC subtypes were identified. Subtype 2 was characterized as lower survival probability and higher risk, along with a more immune-responsive tumor microenvironment. Three genes (IGFBP5, BCL11B, and AKR1B1) screened from aging-related genes were used to establish a prognosis model. The AUC values of the model were greater than 0.669, exhibiting strong prognostic value. In vitro, IGFBP5 overexpression in AGS cells was found to decrease viability, migration, and invasion, alter the cell cycle, and increase aging biomarkers (SA-β-galactosidase, p53, and p21). This analysis uncovered the immune characteristics of two subtypes and aging-related prognosis genes in GC. The prognostic model established for three aging-related genes (IGFBP5, BCL11B, and AKR1B1) demonstrated good prognosis performance, providing a foundation for personalized treatment strategies aimed at GC.
{"title":"Gastric Cancer Immune Subtypes and Prognostic Modeling: Insights from Aging-Related Gene Analysis","authors":"Jian Shen, Minzhe Li","doi":"10.1615/critrevimmunol.2024052391","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052391","url":null,"abstract":"Gastric cancer (GC) is highly heterogeneous and influenced by aging-related factors. This study aimed to improve individualized prognostic assessment of GC by identifying aging-related genes and subtypes. Immune scores of GC samples from GEO and TCGA databases were calculated using ESTIMATE and scored as high immune (IS_high) and low immune (IS_low). ssGSEA was used to analyze immune cell infiltration. Univariate Cox regression was employed to identify prognosis-related genes. LASSO regression analysis was used to construct a prognostic model. GSVA enrichment analysis was applied to determine pathways. CCK-8, wound healing, and Transwell assays tested the proliferation, migration, and invasion of the GC cell line (AGS). Cell cycle and aging were examined using flow cytometry, β-galactosidase staining, and Western blotting. Two aging-related GC subtypes were identified. Subtype 2 was characterized as lower survival probability and higher risk, along with a more immune-responsive tumor microenvironment. Three genes (IGFBP5, BCL11B, and AKR1B1) screened from aging-related genes were used to establish a prognosis model. The AUC values of the model were greater than 0.669, exhibiting strong prognostic value. <i>In vitro</i>, IGFBP5 overexpression in AGS cells was found to decrease viability, migration, and invasion, alter the cell cycle, and increase aging biomarkers (SA-β-galactosidase, p53, and p21). This analysis uncovered the immune characteristics of two subtypes and aging-related prognosis genes in GC. The prognostic model established for three aging-related genes (IGFBP5, BCL11B, and AKR1B1) demonstrated good prognosis performance, providing a foundation for personalized treatment strategies aimed at GC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"232 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139904073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2024051519
Tianyu Lin, Xinli Guo, Qian Du, Wei Liu, Xin Zhong, Suihan Wang, Liping Cao
Objectives. Enhancer of zeste homolog 2 (EZH2) gene has a prognostic role in hepatocellular carcinoma (HCC). This study aimed to identify the role of microRNAs (miRNAs) let-7c-5p by targeting EZH2 in HCC. Methods. We downloaded gene and miRNA RNA-seq data from The Cancer Genome Atlas (TCGA) database. Differences in EZH2 expression between different groups were analyzed and the association of EZH2 expression with HCC prognosis was detected using Cox regression analysis. The miRNA-EZH2-pathway network was constructed. Dual-luciferase reporter assay was performed to detect the hsa-let-7c-5p-EZH2. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8, Wound healing, Transwell, and Flow cytometry, respectively. RT-qPCR and Western blot were used to detect the expression of let-7c-5p and EZH2. Results. EZH2 was upregulated in HCC tumors (P < 0.0001). Cox regression analysis showed that TCGA HCC patients with high EZH2 expression levels showed a short survival time (HR = 1.677, 95% CI 1.316-2.137; P < 0.0001). Seven miRNAs were negatively correlated with EZH2 expression and were significantly downregulated in HCC tumor samples (P < 0.0001), in which hsa-let-7c-5p was associated with prognosis in HCC (HR = 0.849 95% CI 0.739-0.975; P = 0.021). We identified 14 immune cells that showed significant differences in EZH2 high- and low- expression groups. Additionally, let-7c-5p inhibited HCC cell proliferation, migration, and invasion and reversed the promoted effects of EZH2 on HCC cell malignant characteristics. Conclusions. hsa-let-7c-5p-EZH2 significantly suppressed HCC malignant characteristics, which can be used for HCC prognosis.
研究目的泽斯特同源增强子 2（EZH2）基因在肝细胞癌（HCC）中具有预后作用。本研究旨在确定靶向 EZH2 的 microRNA（miRNA）let-7c-5p 在 HCC 中的作用。我们从癌症基因组图谱（TCGA）数据库中下载了基因和miRNA RNA-seq数据。方法：我们从癌症基因组图谱（TCGA）数据库中下载了基因和miRNA RNA-seq数据，分析了不同组间EZH2表达的差异，并使用Cox回归分析检测了EZH2表达与HCC预后的关系。构建了miRNA-EZH2通路网络。采用双荧光素酶报告实验检测 hsa-let-7c-5p-EZH2。细胞增殖、迁移、侵袭和凋亡分别通过 CCK-8、伤口愈合、Transwell 和流式细胞术进行检测。采用 RT-qPCR 和 Western 印迹法检测 let-7c-5p 和 EZH2 的表达。EZH2在HCC肿瘤中上调（P< 0.0001）。Cox回归分析表明，EZH2高表达水平的TCGA HCC患者生存时间较短（HR = 1.677, 95% CI 1.316-2.137; P <0.0001）。7种miRNA与EZH2的表达呈负相关，并在HCC肿瘤样本中显著下调（P <0.0001），其中hsa-let-7c-5p与HCC的预后相关（HR = 0.849 95% CI 0.739-0.975; P = 0.021）。我们发现有 14 种免疫细胞在 EZH2 高表达组和低表达组中存在显著差异。此外，let-7c-5p能抑制HCC细胞的增殖、迁移和侵袭，并逆转EZH2对HCC细胞恶性特征的促进作用。
{"title":"MicroRNA let-7c-5p Alleviates in Hepatocellular Carcinoma by Targeting Enhancer of Zeste Homolog 2: An study intersecting bioinformatic analysis and validated experiments","authors":"Tianyu Lin, Xinli Guo, Qian Du, Wei Liu, Xin Zhong, Suihan Wang, Liping Cao","doi":"10.1615/critrevimmunol.2024051519","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051519","url":null,"abstract":"Objectives. Enhancer of zeste homolog 2 (EZH2) gene has a prognostic role in hepatocellular carcinoma (HCC). This study aimed to identify the role of microRNAs (miRNAs) let-7c-5p by targeting EZH2 in HCC.\u0000Methods. We downloaded gene and miRNA RNA-seq data from The Cancer Genome Atlas (TCGA) database. Differences in EZH2 expression between different groups were analyzed and the association of EZH2 expression with HCC prognosis was detected using Cox regression analysis. The miRNA-EZH2-pathway network was constructed. Dual-luciferase reporter assay was performed to detect the hsa-let-7c-5p-EZH2. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8, Wound healing, Transwell, and Flow cytometry, respectively. RT-qPCR and Western blot were used to detect the expression of let-7c-5p and EZH2.\u0000Results. EZH2 was upregulated in HCC tumors (P < 0.0001). Cox regression analysis showed that TCGA HCC patients with high EZH2 expression levels showed a short survival time (HR = 1.677, 95% CI 1.316-2.137; P < 0.0001). Seven miRNAs were negatively correlated with EZH2 expression and were significantly downregulated in HCC tumor samples (P < 0.0001), in which hsa-let-7c-5p was associated with prognosis in HCC (HR = 0.849 95% CI 0.739-0.975; P = 0.021). We identified 14 immune cells that showed significant differences in EZH2 high- and low- expression groups. Additionally, let-7c-5p inhibited HCC cell proliferation, migration, and invasion and reversed the promoted effects of EZH2 on HCC cell malignant characteristics.\u0000Conclusions. hsa-let-7c-5p-EZH2 significantly suppressed HCC malignant characteristics, which can be used for HCC prognosis.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2024051277
Qianjia Wu, Yang Yang, Chongze Lin
Chronic kidney disease (CKD) is a common disorder related to inflammatory pathways; its effective management remains limited. This study aimed to use bioinformatics analysis to find diagnostic markers that might be therapeutic targets for CKD. CKD microarray datasets were screened from the GEO database and the differentially expressed genes (DEGs) in CKD dataset GSE98603 were analyzed. Gene set variation analysis (GSVA) was used to explore the activity scores of the inflammatory pathways and samples. Algorithms such as weighted gene co-expression network analysis (WGCNA) and Lasso were used to screen CKD diagnostic markers related to inflammation. Then functional enrichment analysis of inflammation-related DEGs was performed. ROC curves were conducted to examine the diagnostic value of inflammation-related hub-genes. Lastly, quantitative real-time PCR further verified the prediction of bioinformatics. A total of 71 inflammation-related DEGs were obtained, of which 5 were hub genes. Enrichment analysis showed that these genes were significantly enriched in inflammation-related pathways (NF-κB, JAK-STAT, and MAPK signaling pathways). ROC curves showed that the 5 CKD diagnostic markers (TIGD7, ACTA2, ACTG2, MAP4K4, and HOXA11) also exhibited good diagnostic value. In addition, TIGD7, ACTA2, ACTG2, and HOXA11 expression was downregulated while MAP4K4 expression was upregulated in LPS-induced HK-2 cells. The present study identified TIGD7, ACTA2, ACTG2, MAP4K4, and HOXA11 as reliable CKD diagnostic markers, thereby providing a basis for further understanding of CKD in clinical treatments.
{"title":"Exploration of Diagnostic Markers Associated with Inflammation in Chronic Kidney Disease Based on WGCNA and Machine Learning","authors":"Qianjia Wu, Yang Yang, Chongze Lin","doi":"10.1615/critrevimmunol.2024051277","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051277","url":null,"abstract":"Chronic kidney disease (CKD) is a common disorder related to inflammatory pathways; its effective management remains limited. This study aimed to use bioinformatics analysis to find diagnostic markers that might be therapeutic targets for CKD. CKD microarray datasets were screened from the GEO database and the differentially expressed genes (DEGs) in CKD dataset GSE98603 were analyzed. Gene set variation analysis (GSVA) was used to explore the activity scores of the inflammatory pathways and samples. Algorithms such as weighted gene co-expression network analysis (WGCNA) and Lasso were used to screen CKD diagnostic markers related to inflammation. Then functional enrichment analysis of inflammation-related DEGs was performed. ROC curves were conducted to examine the diagnostic value of inflammation-related hub-genes. Lastly, quantitative real-time PCR further verified the prediction of bioinformatics. A total of 71 inflammation-related DEGs were obtained, of which 5 were hub genes. Enrichment analysis showed that these genes were significantly enriched in inflammation-related pathways (NF-κB, JAK-STAT, and MAPK signaling pathways). ROC curves showed that the 5 CKD diagnostic markers (TIGD7, ACTA2, ACTG2, MAP4K4, and HOXA11) also exhibited good diagnostic value. In addition, TIGD7, ACTA2, ACTG2, and HOXA11 expression was downregulated while MAP4K4 expression was upregulated in LPS-induced HK-2 cells. The present study identified TIGD7, ACTA2, ACTG2, MAP4K4, and HOXA11 as reliable CKD diagnostic markers, thereby providing a basis for further understanding of CKD in clinical treatments.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"19 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139918676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/critrevimmunol.2024051440
Dalu Yuan, Hailiang Shen, Lina Bai, Menglin Li, Qiujie Ye
Objective: Osteoarthritis (OA) is a prevalent degenerative joint disease that is closely associated with functions of ubiquitination and immune cells, yet the mechanism remains ambiguous. This study aimed to find core ubiquitination-related genes and their correlative immune infiltration in OA using weighted gene co-expression network analysis (WGCNA). Methods: The ubiquitination-related genes, dataset GSE55235 and GSE143514 were obtained from open databases. WGCNA got used to investigate key co-expressed genes. Then, we screened differentially expressed miRNAs by “limma” package in R, and constructed mRNA-miRNA network. We conducted function enrichment analysis on the identified genes. CIBERSORT was then utilized to analysis the relevance between immune infiltration and genes. Lastly, RT-qPCR was further verifying the prediction of bioinformatics. Results: A sum of 144 ubiquitination-related genes in OA were acquired. Enrichment analysis indicated that obtained genes obviously involved in mTOR pathway to regulate the OA development. GRB2 and SEH1L and L-arginine synergistically regulate the mTOR signaling pathway in OA. Moreover, GRB2 and SEH1L were remarkably bound up with immune cell infiltration. Additionally, GRB2 expression was upregulated and SEH1L level was downregulated in the OA development by RT-qPCR experiment. Conclusion: The present study identified GRB2 and SEH1L as key ubiquitination-related genes which were involved in immune infiltration in OA patients, thereby providing new drug targets for OA.
目的：骨关节炎（OA）是一种常见的退行性关节疾病，与泛素化和免疫细胞的功能密切相关，但其机制仍不明确。本研究旨在利用加权基因共表达网络分析（WGCNA）找到 OA 中泛素化相关的核心基因及其相关的免疫浸润：方法：泛素化相关基因数据集GSE55235和GSE143514来自开放数据库。利用 WGCNA 调查关键共表达基因。然后，利用 R 软件包 "limma "筛选差异表达的 miRNA，并构建 mRNA-miRNA 网络。我们对识别出的基因进行了功能富集分析。然后利用 CIBERSORT 分析免疫浸润与基因之间的相关性。最后，RT-qPCR进一步验证了生物信息学的预测结果：结果：共获得了 144 个 OA 中泛素化相关基因。富集分析表明，所获得的基因明显参与了调控 OA 发生的 mTOR 通路。GRB2和SEH1L与L-精氨酸协同调控OA中的mTOR信号通路。此外，GRB2和SEH1L与免疫细胞浸润显著相关。此外，通过RT-qPCR实验发现，GRB2表达上调，SEH1L水平下调：本研究发现 GRB2 和 SEH1L 是参与 OA 患者免疫浸润的泛素化相关关键基因，从而为 OA 的治疗提供了新的药物靶点。
{"title":"Identification of key ubiquitination-related genes and their associated with immune infiltration in osteoarthritis based on mRNA-miRNA network","authors":"Dalu Yuan, Hailiang Shen, Lina Bai, Menglin Li, Qiujie Ye","doi":"10.1615/critrevimmunol.2024051440","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051440","url":null,"abstract":"Objective: Osteoarthritis (OA) is a prevalent degenerative joint disease that is closely associated with functions of ubiquitination and immune cells, yet the mechanism remains ambiguous. This study aimed to find core ubiquitination-related genes and their correlative immune infiltration in OA using weighted gene co-expression network analysis (WGCNA).\u0000Methods: The ubiquitination-related genes, dataset GSE55235 and GSE143514 were obtained from open databases. WGCNA got used to investigate key co-expressed genes. Then, we screened differentially expressed miRNAs by “limma” package in R, and constructed mRNA-miRNA network. We conducted function enrichment analysis on the identified genes. CIBERSORT was then utilized to analysis the relevance between immune infiltration and genes. Lastly, RT-qPCR was further verifying the prediction of bioinformatics.\u0000Results: A sum of 144 ubiquitination-related genes in OA were acquired. Enrichment analysis indicated that obtained genes obviously involved in mTOR pathway to regulate the OA development. GRB2 and SEH1L and L-arginine synergistically regulate the mTOR signaling pathway in OA. Moreover, GRB2 and SEH1L were remarkably bound up with immune cell infiltration. Additionally, GRB2 expression was upregulated and SEH1L level was downregulated in the OA development by RT-qPCR experiment.\u0000Conclusion: The present study identified GRB2 and SEH1L as key ubiquitination-related genes which were involved in immune infiltration in OA patients, thereby providing new drug targets for OA.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"33 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139517053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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