Pub Date : 2024-02-13DOI: 10.2174/0115665232284076240207073542
Songzi Zhang, Wenjie Hu, Changjun Lv, Xiaodong Song
: Pulmonary fibrosis is a class of fibrosing interstitial lung diseases caused by many pathogenic factors inside and outside the lung, with unknown mechanisms and without effective treatment. Therefore, a comprehensive understanding of the molecular mechanism implicated in pulmonary fibrosis pathogenesis is urgently needed to develop new and effective measures. Although circRNAs have been widely acknowledged as new contributors to the occurrence and development of diseases, only a small number of circRNAs have been functionally characterized in pulmonary fibrosis. Here, we systematically review the biogenesis and functions of circRNAs and focus on how circRNAs participate in pulmonary fibrogenesis by influencing various cell fates. Meanwhile, we analyze the current exploration of circRNAs as a diagnostic biomarker, vaccine, and therapeutic target in pulmonary fibrosis and objectively discuss the challenges of circRNA-based therapy for pulmonary fibrosis. We hope that the review of the implication of circRNAs will provide new insights into the development circRNA-based approaches to treat pulmonary fibrosis.
{"title":"Biogenesis and Function of circRNAs in Pulmonary Fibrosis","authors":"Songzi Zhang, Wenjie Hu, Changjun Lv, Xiaodong Song","doi":"10.2174/0115665232284076240207073542","DOIUrl":"https://doi.org/10.2174/0115665232284076240207073542","url":null,"abstract":": Pulmonary fibrosis is a class of fibrosing interstitial lung diseases caused by many pathogenic factors inside and outside the lung, with unknown mechanisms and without effective treatment. Therefore, a comprehensive understanding of the molecular mechanism implicated in pulmonary fibrosis pathogenesis is urgently needed to develop new and effective measures. Although circRNAs have been widely acknowledged as new contributors to the occurrence and development of diseases, only a small number of circRNAs have been functionally characterized in pulmonary fibrosis. Here, we systematically review the biogenesis and functions of circRNAs and focus on how circRNAs participate in pulmonary fibrogenesis by influencing various cell fates. Meanwhile, we analyze the current exploration of circRNAs as a diagnostic biomarker, vaccine, and therapeutic target in pulmonary fibrosis and objectively discuss the challenges of circRNA-based therapy for pulmonary fibrosis. We hope that the review of the implication of circRNAs will provide new insights into the development circRNA-based approaches to treat pulmonary fibrosis.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770762","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 : 2024-02-07DOI: 10.2174/0115665232294568240201073417
Tianming Jiang, Jie Zheng, Nana Li, Xiaodong Li, Jixing He, Junde Zhou, Boshi Sun, Qiang Chi
Introduction: Crohn's disease (CD) and colorectal cancer (CRC) represent a group of intestinal disorders characterized by intricate pathogenic mechanisms linked to the disruption of intestinal immune homeostasis. Therefore, comprehending the immune response mechanisms in both categories of intestinal disorders is of paramount significance in the prevention and treatment of these debilitating intestinal ailments. Method: In this study, we conducted single-cell analysis on paired samples obtained from primary colorectal tumors and individuals with Crohn's disease, which was aimed at deciphering the factors influencing the composition of the intestinal immune microenvironment. By aligning T cells across different tissues, we identified various T cell subtypes, such as γδ T cell, NK T cell, and regulatory T (Treg) cell, which maintained immune system homeostasis and were confirmed in enrichment analyses. Subsequently, we generated pseudo-time trajectories for subclusters of T cells in both syndromes to delineate their differentiation patterns and identify key driver genes. Result: Furthermore, cellular communication and transcription factor regulatory networks are all essential components of the intricate web of mechanisms that regulate intestinal immune homeostasis. The identified complex cellular interaction suggested potential T-lineage immunotherapeutic targets against epithelial cells with high copy number variation (CNV) levels in CD and CRC. Conclusion: Finally, the analysis of regulon networks revealed several promising candidates for cell-specific transcription factors (TFs). This study focused on the immune molecular mechanism under intestinal diseases. It contributed to the novel insight of depicting a detailed immune landscape and revealing T-cell responding mechanisms in CD and CRC.
导言:克罗恩病(CD)和结肠直肠癌(CRC)是一类肠道疾病,其特点是错综复杂的致病机制与肠道免疫平衡的破坏有关。因此,了解这两类肠道疾病的免疫反应机制对于预防和治疗这些使人衰弱的肠道疾病具有重要意义。研究方法在这项研究中,我们对原发性结直肠肿瘤和克罗恩病患者的配对样本进行了单细胞分析,旨在破译影响肠道免疫微环境组成的因素。通过对不同组织的T细胞进行比对,我们发现了各种T细胞亚型,如γδ T细胞、NK T细胞和调节性T(Treg)细胞,它们维持着免疫系统的平衡,并在富集分析中得到了证实。随后,我们为这两种综合征中的T细胞亚群生成了伪时间轨迹,以描述它们的分化模式并确定关键驱动基因。结果此外,细胞通讯和转录因子调控网络都是调节肠道免疫平衡的复杂机制网络的重要组成部分。已确定的复杂细胞相互作用为针对 CD 和 CRC 中具有高拷贝数变异 (CNV) 水平的上皮细胞的 T 线免疫治疗提供了潜在靶点。结论最后,对调控子网络的分析发现了几个有希望的候选细胞特异性转录因子(TFs)。这项研究的重点是肠道疾病的免疫分子机制。该研究为描绘CD和CRC的详细免疫图谱和揭示T细胞应答机制提供了新的视角。
{"title":"Dissecting the Mechanisms of Intestinal Immune Homeostasis by Analyzing T-Cell Immune Response in Crohn's Disease and Colorectal Cancer","authors":"Tianming Jiang, Jie Zheng, Nana Li, Xiaodong Li, Jixing He, Junde Zhou, Boshi Sun, Qiang Chi","doi":"10.2174/0115665232294568240201073417","DOIUrl":"https://doi.org/10.2174/0115665232294568240201073417","url":null,"abstract":"Introduction: Crohn's disease (CD) and colorectal cancer (CRC) represent a group of intestinal disorders characterized by intricate pathogenic mechanisms linked to the disruption of intestinal immune homeostasis. Therefore, comprehending the immune response mechanisms in both categories of intestinal disorders is of paramount significance in the prevention and treatment of these debilitating intestinal ailments. Method: In this study, we conducted single-cell analysis on paired samples obtained from primary colorectal tumors and individuals with Crohn's disease, which was aimed at deciphering the factors influencing the composition of the intestinal immune microenvironment. By aligning T cells across different tissues, we identified various T cell subtypes, such as γδ T cell, NK T cell, and regulatory T (Treg) cell, which maintained immune system homeostasis and were confirmed in enrichment analyses. Subsequently, we generated pseudo-time trajectories for subclusters of T cells in both syndromes to delineate their differentiation patterns and identify key driver genes. Result: Furthermore, cellular communication and transcription factor regulatory networks are all essential components of the intricate web of mechanisms that regulate intestinal immune homeostasis. The identified complex cellular interaction suggested potential T-lineage immunotherapeutic targets against epithelial cells with high copy number variation (CNV) levels in CD and CRC. Conclusion: Finally, the analysis of regulon networks revealed several promising candidates for cell-specific transcription factors (TFs). This study focused on the immune molecular mechanism under intestinal diseases. It contributed to the novel insight of depicting a detailed immune landscape and revealing T-cell responding mechanisms in CD and CRC.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770761","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 : 2024-02-07DOI: 10.2174/0115665232273077240104045022
Sushmitha Sriramulu, Sarubala Malayaperumal, Antara Banerjee, Muralidharan Anbalagan, Makalakshmi M K, Rajesh Kanna NR, Xingyi Liu, Hong Zhang, Guang Hu, Xiao-Feng Sun, Surajit Pathak
Background: Astrocyte elevated gene-1 (AEG-1) is overexpressed in various malignancies. Exostosin-1 (EXT-1), a tumor suppressor, is an intermediate for malignant tumors. Understanding the mechanism behind the interaction between AEG-1 and EXT-1 may provide insights into colon cancer metastasis. Methods: AOM/DSS was used to induce tumor in BALB/c mice. Using an in vivo-jetPEI transfection reagent, transient transfection of AEG-1 and EXT-1 siRNAs were achieved. Histological scoring, immunohistochemical staining, and gene expression studies were performed from excised tissues. Data from the Cancer Genomic Atlas and GEO databases were obtained to identify the expression status of AEG-1 and itsassociation with the survival. Results: In BALB/c mice, the AOM+DSS treated mice developed necrotic, inflammatory and dysplastic changes in the colon with definite clinical symptoms such as loss of goblet cells, colon shortening, and collagen deposition. Administration of AEG-1 siRNA resulted in a substantial decrease in the disease activity index. Mice treated with EXT-1 siRNA showed diffusely reduced goblet cells. In vivo investigations revealed that PTCH-1 activity was influenced by upstream gene AEG-1, which in turn may affect EXT-1 activity. Data from The Cancer Genomic Atlas and GEO databases confirmed the upregulation of AEG-1 and downregulation of EXT-1 in cancer patients. Conclusions: This study revealed that AEG-1 silencing might alter EXT-1 expression indirectly through PTCH-1, influencing cell-ECM interactions, and decreasing dysplastic changes, proliferation and invasion.
{"title":"AEG-1 as a Novel Therapeutic Target in Colon Cancer: A Study from Silencing AEG-1 in BALB/c Mice to Large Data Analysis","authors":"Sushmitha Sriramulu, Sarubala Malayaperumal, Antara Banerjee, Muralidharan Anbalagan, Makalakshmi M K, Rajesh Kanna NR, Xingyi Liu, Hong Zhang, Guang Hu, Xiao-Feng Sun, Surajit Pathak","doi":"10.2174/0115665232273077240104045022","DOIUrl":"https://doi.org/10.2174/0115665232273077240104045022","url":null,"abstract":"Background: Astrocyte elevated gene-1 (AEG-1) is overexpressed in various malignancies. Exostosin-1 (EXT-1), a tumor suppressor, is an intermediate for malignant tumors. Understanding the mechanism behind the interaction between AEG-1 and EXT-1 may provide insights into colon cancer metastasis. Methods: AOM/DSS was used to induce tumor in BALB/c mice. Using an in vivo-jetPEI transfection reagent, transient transfection of AEG-1 and EXT-1 siRNAs were achieved. Histological scoring, immunohistochemical staining, and gene expression studies were performed from excised tissues. Data from the Cancer Genomic Atlas and GEO databases were obtained to identify the expression status of AEG-1 and itsassociation with the survival. Results: In BALB/c mice, the AOM+DSS treated mice developed necrotic, inflammatory and dysplastic changes in the colon with definite clinical symptoms such as loss of goblet cells, colon shortening, and collagen deposition. Administration of AEG-1 siRNA resulted in a substantial decrease in the disease activity index. Mice treated with EXT-1 siRNA showed diffusely reduced goblet cells. In vivo investigations revealed that PTCH-1 activity was influenced by upstream gene AEG-1, which in turn may affect EXT-1 activity. Data from The Cancer Genomic Atlas and GEO databases confirmed the upregulation of AEG-1 and downregulation of EXT-1 in cancer patients. Conclusions: This study revealed that AEG-1 silencing might alter EXT-1 expression indirectly through PTCH-1, influencing cell-ECM interactions, and decreasing dysplastic changes, proliferation and invasion.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770758","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}