Cancer remains a major global health challenge, with the persistence of cancer stem cells (CSCs) contributing to treatment resistance and relapse. Despite advancements in cancer therapy, targeting CSCs presents a significant hurdle. Non-thermal gas plasma, also known as CAP, represents an innovative cancer treatment. It has recently gained attention for its often found to be selective, immunogenic, and potent anti-cancer properties. CAP is composed of a collection of transient, high-energy, and physically and chemically active entities, such as reactive oxygen species (ROS). It is acknowledged that the latter are responsible for a major portion of biomedical CAP effects. The dynamic interplay of CAP-derived ROS and other components contributes to the unique and versatile properties of CAP, enabling it to interact with biological systems and elicit various therapeutic effects, including its potential in cancer treatment. While CAP has shown promise in various cancer types, its application against CSCs is relatively unexplored. This review assesses the potential of CAP as a therapeutic strategy for targeting CSCs, focusing on its ability to regulate cellular states and achieve redox homeostasis. This is done by providing an overview of CSC characteristics and demonstrating recent findings on CAP's efficacy in targeting these cells. By contributing insights into the unique attributes of CSCs and the potential of CAP, this work contributes to an advanced understanding of innovative oncology strategies.
癌症仍然是全球健康的一大挑战,癌症干细胞(CSCs)的持续存在导致了治疗耐药性和复发。尽管癌症治疗取得了进展,但针对癌干细胞的治疗仍是一个重大障碍。非热气体等离子体(又称CAP)是一种创新的癌症治疗方法。最近,它因其经常被发现具有选择性、免疫原性和强效抗癌特性而备受关注。CAP 由一系列瞬时、高能、物理和化学活性实体组成,如活性氧(ROS)。众所周知,后者是 CAP 生物医学效应的主要原因。CAP 衍生的 ROS 和其他成分之间的动态相互作用造就了 CAP 独特而多变的特性,使其能够与生物系统相互作用并激发各种治疗效果,包括在癌症治疗中的潜力。虽然 CAP 已在多种癌症类型中显示出前景,但其对 CSCs 的应用还相对缺乏探索。本综述评估了 CAP 作为针对 CSCs 的治疗策略的潜力,重点关注其调节细胞状态和实现氧化还原平衡的能力。本文概述了 CSC 的特征,并展示了 CAP 在靶向这些细胞方面的最新研究成果。通过深入了解 CSCs 的独特属性和 CAP 的潜力,这项研究有助于加深对创新肿瘤学策略的理解。
{"title":"Reactive oxygen species from non-thermal gas plasma (CAP): implication for targeting cancer stem cells.","authors":"Amirhesam Babajani, Afshin Eftekharinasab, Sander Bekeschus, Hassan Mehdian, Faezeh Vakhshiteh, Zahra Madjd","doi":"10.1186/s12935-024-03523-x","DOIUrl":"10.1186/s12935-024-03523-x","url":null,"abstract":"<p><p>Cancer remains a major global health challenge, with the persistence of cancer stem cells (CSCs) contributing to treatment resistance and relapse. Despite advancements in cancer therapy, targeting CSCs presents a significant hurdle. Non-thermal gas plasma, also known as CAP, represents an innovative cancer treatment. It has recently gained attention for its often found to be selective, immunogenic, and potent anti-cancer properties. CAP is composed of a collection of transient, high-energy, and physically and chemically active entities, such as reactive oxygen species (ROS). It is acknowledged that the latter are responsible for a major portion of biomedical CAP effects. The dynamic interplay of CAP-derived ROS and other components contributes to the unique and versatile properties of CAP, enabling it to interact with biological systems and elicit various therapeutic effects, including its potential in cancer treatment. While CAP has shown promise in various cancer types, its application against CSCs is relatively unexplored. This review assesses the potential of CAP as a therapeutic strategy for targeting CSCs, focusing on its ability to regulate cellular states and achieve redox homeostasis. This is done by providing an overview of CSC characteristics and demonstrating recent findings on CAP's efficacy in targeting these cells. By contributing insights into the unique attributes of CSCs and the potential of CAP, this work contributes to an advanced understanding of innovative oncology strategies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-20DOI: 10.1186/s12935-024-03513-z
Vivek K Kashyap, Prashanth K B Nagesh, Ajay K Singh, Andrew Massey, Godwin P Darkwah, Aaron George, Sheema Khan, Bilal B Hafeez, Nadeem Zafar, Santosh Kumar, Namita Sinha, Murali M Yallapu, Meena Jaggi, Subhash C Chauhan
Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation.
Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models.
Results: Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment.
Conclusions: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment.
{"title":"Curcumin attenuates smoking and drinking activated NF-κB/IL-6 inflammatory signaling axis in cervical cancer.","authors":"Vivek K Kashyap, Prashanth K B Nagesh, Ajay K Singh, Andrew Massey, Godwin P Darkwah, Aaron George, Sheema Khan, Bilal B Hafeez, Nadeem Zafar, Santosh Kumar, Namita Sinha, Murali M Yallapu, Meena Jaggi, Subhash C Chauhan","doi":"10.1186/s12935-024-03513-z","DOIUrl":"10.1186/s12935-024-03513-z","url":null,"abstract":"<p><strong>Background: </strong>High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation.</p><p><strong>Methods: </strong>The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models.</p><p><strong>Results: </strong>Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment.</p><p><strong>Conclusions: </strong>These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive.
Methods: The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry.
Results: In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB.
Conclusions: The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.
{"title":"CD74 is a potential biomarker predicting the response to immune checkpoint blockade.","authors":"Wen-Qi Shi, Dan-Xun Chen, Ze-Sen Du, Chun-Peng Liu, Tian-Tian Zhai, Feng Pan, Hai-Lu Chen, Wei-Nan Liao, Shao-Hong Wang, Jun-Hui Fu, Si-Qi Qiu, Zhi-Yong Wu","doi":"10.1186/s12935-024-03524-w","DOIUrl":"https://doi.org/10.1186/s12935-024-03524-w","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive.</p><p><strong>Methods: </strong>The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry.</p><p><strong>Results: </strong>In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB.</p><p><strong>Conclusions: </strong>The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1186/s12935-024-03521-z
Yang Zhou, Zhenzhen Luo, Jinfeng Guo, Lixia Wu, Xiaoli Zhou, Jun Jie Huang, Daijia Huang, Li Xiao, Qiuhua Duan, Jianhua Chang, Libao Gong, Junjie Hang
Background: Sp1, a transcription factor, regulates essential cellular processes and plays important tumorigenic roles across diverse cancers. However, comprehensive pan-cancer analyses of its expression and potential immunomodulatory roles remain unexplored.
Methods: Utilizing bioinformatics tools and public datasets, we examined the expression of Sp1 across normal tissues, tumors, and immune cells, and screened for pre- and post-transcriptional modifications, including genetic alterations, DNA methylation, and protein phosphorylation, affecting its expression or function. The association of Sp1 expression with immune cell infiltration, tumor mutational burden, and immune checkpoint signaling was also investigated. Single-cell transcriptome data was used to assess Sp1 expression in immune cells in gastric cancer (GC), and findings were corroborated using immunohistochemistry and multiplex immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC patients receiving immunotherapy was evaluated with Cox regression models.
Results: Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in GC. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Significant correlations between Sp1 levels and CD8+ T cell and the M1 phenotype of tumor-associated macrophages were further detected upon multiplex immunofluorescence in GC samples. Interestingly, we verified that GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.
Conclusions: Our pan-cancer analysis sheds light on the multifaceted role of Sp1 in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for patients with GC undergoing immunotherapy.
{"title":"Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer.","authors":"Yang Zhou, Zhenzhen Luo, Jinfeng Guo, Lixia Wu, Xiaoli Zhou, Jun Jie Huang, Daijia Huang, Li Xiao, Qiuhua Duan, Jianhua Chang, Libao Gong, Junjie Hang","doi":"10.1186/s12935-024-03521-z","DOIUrl":"https://doi.org/10.1186/s12935-024-03521-z","url":null,"abstract":"<p><strong>Background: </strong>Sp1, a transcription factor, regulates essential cellular processes and plays important tumorigenic roles across diverse cancers. However, comprehensive pan-cancer analyses of its expression and potential immunomodulatory roles remain unexplored.</p><p><strong>Methods: </strong>Utilizing bioinformatics tools and public datasets, we examined the expression of Sp1 across normal tissues, tumors, and immune cells, and screened for pre- and post-transcriptional modifications, including genetic alterations, DNA methylation, and protein phosphorylation, affecting its expression or function. The association of Sp1 expression with immune cell infiltration, tumor mutational burden, and immune checkpoint signaling was also investigated. Single-cell transcriptome data was used to assess Sp1 expression in immune cells in gastric cancer (GC), and findings were corroborated using immunohistochemistry and multiplex immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC patients receiving immunotherapy was evaluated with Cox regression models.</p><p><strong>Results: </strong>Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in GC. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Significant correlations between Sp1 levels and CD8+ T cell and the M1 phenotype of tumor-associated macrophages were further detected upon multiplex immunofluorescence in GC samples. Interestingly, we verified that GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.</p><p><strong>Conclusions: </strong>Our pan-cancer analysis sheds light on the multifaceted role of Sp1 in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for patients with GC undergoing immunotherapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies.
{"title":"RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.","authors":"Yidi Ning, Minying Zheng, Yue Zhang, Yuqi Jiao, Jiangping Wang, Shiwu Zhang","doi":"10.1186/s12935-024-03519-7","DOIUrl":"https://doi.org/10.1186/s12935-024-03519-7","url":null,"abstract":"<p><p>The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1186/s12935-024-03482-3
Xi Wang, Hengyuan Gao, Wenjun Pu, Zhipeng Zeng, Nan Xu, Xunpeng Luo, Donge Tang, Yong Dai
Background: Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.
Methods: We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.
Results: Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.
Conclusions: Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.
{"title":"Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis.","authors":"Xi Wang, Hengyuan Gao, Wenjun Pu, Zhipeng Zeng, Nan Xu, Xunpeng Luo, Donge Tang, Yong Dai","doi":"10.1186/s12935-024-03482-3","DOIUrl":"https://doi.org/10.1186/s12935-024-03482-3","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.</p><p><strong>Methods: </strong>We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.</p><p><strong>Results: </strong>Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.</p><p><strong>Conclusions: </strong>Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1186/s12935-024-03522-y
Fei Cao, Qian You, Feng Zhu, Yu Zhang
Low-dose CT (LDCT) is increasingly recognized as the preferred method for detecting pulmonary nodules. However, distinguishing whether a nodule is benign or malignant often necessitates repeated scans or invasive tissue sampling procedures. Therefore, there is a pressing need for non-invasive techniques to minimize unnecessary interventions. This study aim to investigate the expression profile of exosomal snoRNA in the serum of patients with benign and malignant pulmonary nodules. We identified a total of 278 snoRNAs in serum exosomes, revealing significant differences in snoRNA levels between patients with malignant and benign nodules. Specifically, the upregulated snoRNAs U78 and U37 were validated through qRT-PCR and were found significantly elevated in the serum of patients with malignant pulmonary nodules, positioning them as promising biomarkers for the early detection of lung cancer. This study underscores the potential of serum exosomal U78 and U37 as critical tools for assessing the risk of pulmonary nodules identified through CT screening.
{"title":"Serum exosomal small nucleolar RNA (snoRNA) signatures as a predictive biomarker for benign and malignant pulmonary nodules.","authors":"Fei Cao, Qian You, Feng Zhu, Yu Zhang","doi":"10.1186/s12935-024-03522-y","DOIUrl":"https://doi.org/10.1186/s12935-024-03522-y","url":null,"abstract":"<p><p>Low-dose CT (LDCT) is increasingly recognized as the preferred method for detecting pulmonary nodules. However, distinguishing whether a nodule is benign or malignant often necessitates repeated scans or invasive tissue sampling procedures. Therefore, there is a pressing need for non-invasive techniques to minimize unnecessary interventions. This study aim to investigate the expression profile of exosomal snoRNA in the serum of patients with benign and malignant pulmonary nodules. We identified a total of 278 snoRNAs in serum exosomes, revealing significant differences in snoRNA levels between patients with malignant and benign nodules. Specifically, the upregulated snoRNAs U78 and U37 were validated through qRT-PCR and were found significantly elevated in the serum of patients with malignant pulmonary nodules, positioning them as promising biomarkers for the early detection of lung cancer. This study underscores the potential of serum exosomal U78 and U37 as critical tools for assessing the risk of pulmonary nodules identified through CT screening.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1186/s12935-024-03509-9
Yu Chen, Shen Chen, Zhenkai Wu, Quan Cheng, Dan Ji
Background: Hypoxia-related genes are linked to the prognosis of various solid malignant tumors. However, the role of hypoxia-related long non-coding RNAs (HRLs) in uveal melanoma (UVM) remains unclear. This study aimed to identify HRLs associated with UVM prognosis and develop a novel risk signature to predict patient outcomes.
Methods: Data from 80 UVM samples were obtained from The Cancer Genome Atlas. Prognostic HRLs were screened using Cox univariate and Pearson correlation analyses. HRL signature were constructed using Lasso analysis, and gene enrichment analysis was performed to explore the association between HRLs and immune features. Cell Counting Kit-8 assay was used to measure the propagation of human uveal melanoma (MuM2B) cells, while tumor invasion and migration were evaluated using Transwell and wound-healing experiments. Inflammatory factors and macrophage polarization were evaluated using quantitative PCR.
Results: In total, 621 prognostic HRLs were screened and constructed in 12 HRLs. The risk score showed a significant correlation with the survival time of patients with UVM. Additionally, HRL correlated with diverse key immune checkpoints, revealing possible targets for immunotherapy. Immune-related pathways were highly enriched in the high-risk group. LINC02367, a protective HRL, was associated with the tumor microenvironment and survival time of patients with UVM. In vitro, LINC02367 significantly influenced MuM2B proliferation and migration. It also modulated macrophage polarization by regulating inflammatory factor levels, thereby affecting the immune microenvironment.
Conclusions: We developed a novel HRL signature to predict prognosis in patients with UVM. HRLs are potential biomarkers and therapeutic targets for the treatment of UVM.
背景:缺氧相关基因与各种实体恶性肿瘤的预后有关。然而,缺氧相关长非编码 RNA(HRLs)在葡萄膜黑色素瘤(UVM)中的作用仍不清楚。本研究旨在鉴定与葡萄膜黑色素瘤预后相关的HRLs,并开发一种新的风险特征来预测患者的预后:方法:从癌症基因组图谱(The Cancer Genome Atlas)中获得了80个UVM样本的数据。利用Cox单变量分析和Pearson相关分析筛选出预后相关的HRL。利用Lasso分析构建了HRL特征,并进行了基因富集分析,以探索HRL与免疫特征之间的关联。细胞计数试剂盒-8测定了人葡萄膜黑色素瘤(MuM2B)细胞的繁殖,Transwell和伤口愈合实验评估了肿瘤的侵袭和迁移。利用定量 PCR 评估了炎症因子和巨噬细胞极化:结果:共筛选出621个预后HRL,并在12个HRL中构建了预后HRL。风险评分与 UVM 患者的生存时间有明显相关性。此外,HRL与多种关键免疫检查点相关,揭示了免疫疗法的可能靶点。免疫相关通路在高风险组中高度富集。LINC02367是一种保护性HRL,它与UVM患者的肿瘤微环境和生存时间有关。在体外,LINC02367能显著影响MuM2B的增殖和迁移。它还通过调节炎症因子水平来调节巨噬细胞的极化,从而影响免疫微环境:我们发现了一种新的HRL特征,可用于预测紫癜患者的预后。HRL是治疗紫癜的潜在生物标志物和治疗靶点。
{"title":"Hypoxia-related lncRNA correlates with prognosis and immune microenvironment in uveal melanoma.","authors":"Yu Chen, Shen Chen, Zhenkai Wu, Quan Cheng, Dan Ji","doi":"10.1186/s12935-024-03509-9","DOIUrl":"10.1186/s12935-024-03509-9","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia-related genes are linked to the prognosis of various solid malignant tumors. However, the role of hypoxia-related long non-coding RNAs (HRLs) in uveal melanoma (UVM) remains unclear. This study aimed to identify HRLs associated with UVM prognosis and develop a novel risk signature to predict patient outcomes.</p><p><strong>Methods: </strong>Data from 80 UVM samples were obtained from The Cancer Genome Atlas. Prognostic HRLs were screened using Cox univariate and Pearson correlation analyses. HRL signature were constructed using Lasso analysis, and gene enrichment analysis was performed to explore the association between HRLs and immune features. Cell Counting Kit-8 assay was used to measure the propagation of human uveal melanoma (MuM2B) cells, while tumor invasion and migration were evaluated using Transwell and wound-healing experiments. Inflammatory factors and macrophage polarization were evaluated using quantitative PCR.</p><p><strong>Results: </strong>In total, 621 prognostic HRLs were screened and constructed in 12 HRLs. The risk score showed a significant correlation with the survival time of patients with UVM. Additionally, HRL correlated with diverse key immune checkpoints, revealing possible targets for immunotherapy. Immune-related pathways were highly enriched in the high-risk group. LINC02367, a protective HRL, was associated with the tumor microenvironment and survival time of patients with UVM. In vitro, LINC02367 significantly influenced MuM2B proliferation and migration. It also modulated macrophage polarization by regulating inflammatory factor levels, thereby affecting the immune microenvironment.</p><p><strong>Conclusions: </strong>We developed a novel HRL signature to predict prognosis in patients with UVM. HRLs are potential biomarkers and therapeutic targets for the treatment of UVM.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-07DOI: 10.1186/s12935-024-03518-8
Shuhong Yu, Siyu Wang, Xuanyu Wang, Ximing Xu
The extracellular matrix (ECM) is a complex, dynamic network of multiple macromolecules that serve as a crucial structural and physical scaffold for neighboring cells. In the tumor microenvironment (TME), ECM proteins play a significant role in mediating cellular communication between cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). Revealing the ECM modification of the TME necessitates the intricate signaling cascades that transpire among diverse cell populations and ECM proteins. The advent of single-cell sequencing has enabled the identification and refinement of specific cellular subpopulations, which has substantially enhanced our comprehension of the intricate milieu and given us a high-resolution perspective on the diversity of ECM proteins. However, it is essential to integrate single-cell data and establish a coherent framework. In this regard, we present a comprehensive review of the relationships among ECM, TAMs, and CAFs. This encompasses insights into the ECM proteins released by TAMs and CAFs, signaling integration in the TAM-ECM-CAF axis, and the potential applications and limitations of targeted therapies for CAFs. This review serves as a reliable resource for focused therapeutic strategies while highlighting the crucial role of ECM proteins as intermediates in the TME.
{"title":"The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.","authors":"Shuhong Yu, Siyu Wang, Xuanyu Wang, Ximing Xu","doi":"10.1186/s12935-024-03518-8","DOIUrl":"https://doi.org/10.1186/s12935-024-03518-8","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is a complex, dynamic network of multiple macromolecules that serve as a crucial structural and physical scaffold for neighboring cells. In the tumor microenvironment (TME), ECM proteins play a significant role in mediating cellular communication between cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). Revealing the ECM modification of the TME necessitates the intricate signaling cascades that transpire among diverse cell populations and ECM proteins. The advent of single-cell sequencing has enabled the identification and refinement of specific cellular subpopulations, which has substantially enhanced our comprehension of the intricate milieu and given us a high-resolution perspective on the diversity of ECM proteins. However, it is essential to integrate single-cell data and establish a coherent framework. In this regard, we present a comprehensive review of the relationships among ECM, TAMs, and CAFs. This encompasses insights into the ECM proteins released by TAMs and CAFs, signaling integration in the TAM-ECM-CAF axis, and the potential applications and limitations of targeted therapies for CAFs. This review serves as a reliable resource for focused therapeutic strategies while highlighting the crucial role of ECM proteins as intermediates in the TME.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}