Pub Date : 2025-10-22DOI: 10.1016/j.adcanc.2025.100158
Maryam Motallebinezhad , Ali Faravash , Mohammad Ghasemian , Zahra Tajik , Mohsen Ahmadi , Solat Eslami , Soudeh Ghafouri-Fard
As an imidazotetrazine derived from the alkylating substance dacarbazine, Temozolomide (TMZ) is commonly used as the routine chemotherapy for new cases of glioblastoma multiforme (GBM). It substantially improves the clinical outcome of patients. But, resistance to TMZ is regarded as a principal impediment in the postgenomic years of GBM management. Recent investigations showed the critical roles of lncRNAs, miRNAs and circRNAs and their interactions in GBM treatment. Remarkably, several miRNAs, such as miR-125b, miR-30b-3p, miR-24-3p, miR-590, miR-125b, and miR-7-5p regulate activity of glioma stem cells. Besides, a number of miRNAs, namely miR-370-3p, miR-198, miR-486-3p, miR-29c, miR-130a, miR-181 d, miR-198, miR-182-5p and miR-370-3p regulate expression of the DNA repair protein MGMT. Most of lncRNAs and circRNAs exert their role on TMZ resistance through sponging miRNAs. Notably, these transcripts have revolutionized the understanding about GBM pathogenesis and application of personalized medicine for this cancer. This review concentrates on the importance of these transcripts in resistance to TMZ in GBM patients.
{"title":"Temozolomide resistance in glioblastoma: a non-coding RNA viewpoint","authors":"Maryam Motallebinezhad , Ali Faravash , Mohammad Ghasemian , Zahra Tajik , Mohsen Ahmadi , Solat Eslami , Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100158","DOIUrl":"10.1016/j.adcanc.2025.100158","url":null,"abstract":"<div><div>As an imidazotetrazine derived from the alkylating substance dacarbazine, Temozolomide (TMZ) is commonly used as the routine chemotherapy for new cases of glioblastoma multiforme (GBM). It substantially improves the clinical outcome of patients. But, resistance to TMZ is regarded as a principal impediment in the postgenomic years of GBM management. Recent investigations showed the critical roles of lncRNAs, miRNAs and circRNAs and their interactions in GBM treatment. Remarkably, several miRNAs, such as miR-125b, miR-30b-3p, miR-24-3p, miR-590, miR-125b, and miR-7-5p regulate activity of glioma stem cells. Besides, a number of miRNAs, namely miR-370-3p, miR-198, miR-486-3p, miR-29c, miR-130a, miR-181 d, miR-198, miR-182-5p and miR-370-3p regulate expression of the DNA repair protein MGMT. Most of lncRNAs and circRNAs exert their role on TMZ resistance through sponging miRNAs. Notably, these transcripts have revolutionized the understanding about GBM pathogenesis and application of personalized medicine for this cancer. This review concentrates on the importance of these transcripts in resistance to TMZ in GBM patients.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100158"},"PeriodicalIF":3.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-03DOI: 10.1016/j.adcanc.2025.100155
Alireza Soleimani , Amir Sadeghi , Zahra Fazeli , Solat Eslami , Mohammad Rahmanian , Binazir Khanabadi , Soudeh Ghafouri-Fard , Mir Davood Omrani
The Wnt signaling cascade is crucial for diverse biological processes, including cell cycle regulation, inflammation, embryonic development, and tumorigenesis. The present study investigates the expression of TSPOAP1-AS1, TMEM147-AS1, and FOXP4-AS1 lncRNAs, along with RNF43, all of which are associated with the Wnt/β-catenin signaling pathway, in colorectal cancer (CRC) samples compared to adjacent normal tissues (ANTs). RNF43 was significantly overexpressed in CRC samples, with a median 2.34-fold increase relative to normal tissues (P value = 0.04). In contrast, the lncRNA TSPOAP1-AS1 was markedly down-regulated in tumors, showing a median 0.42-fold reduction (P value = 0.03). The remaining two lncRNAs—TMEM147-AS1 and FOXP4-AS1—were also significantly elevated, exhibiting median fold-changes of 2.94-fold (P value < 0.0001) and 2.02-fold (P value = 0.003), respectively. All four transcripts achieved exceptionally high specificity (97.5–100 %) but only moderate sensitivity (29.3–56.1 %) for discrimination of CRC samples from ANTS, reflecting their stringent discrimination of ANTs at the expense of missing a subset of tumors. Taken together, our results revealed a coordinated dysregulation of Wnt-related genes in CRC, i.e. loss of TSPOAP1-AS1 alongside gain of RNF43, TMEM147-AS1, and FOXP4-AS1 expression, highlighting their potential as complementary biomarkers.
{"title":"Integrated dysregulation of RNF43 and associated lncRNAs reveals transcriptional remodeling in colorectal carcinoma","authors":"Alireza Soleimani , Amir Sadeghi , Zahra Fazeli , Solat Eslami , Mohammad Rahmanian , Binazir Khanabadi , Soudeh Ghafouri-Fard , Mir Davood Omrani","doi":"10.1016/j.adcanc.2025.100155","DOIUrl":"10.1016/j.adcanc.2025.100155","url":null,"abstract":"<div><div>The Wnt signaling cascade is crucial for diverse biological processes, including cell cycle regulation, inflammation, embryonic development, and tumorigenesis. The present study investigates the expression of TSPOAP1-AS1, TMEM147-AS1, and FOXP4-AS1 lncRNAs, along with RNF43, all of which are associated with the Wnt/β-catenin signaling pathway, in colorectal cancer (CRC) samples compared to adjacent normal tissues (ANTs). RNF43 was significantly overexpressed in CRC samples, with a median 2.34-fold increase relative to normal tissues (P value = 0.04). In contrast, the lncRNA TSPOAP1-AS1 was markedly down-regulated in tumors, showing a median 0.42-fold reduction (P value = 0.03). The remaining two lncRNAs—TMEM147-AS1 and FOXP4-AS1—were also significantly elevated, exhibiting median fold-changes of 2.94-fold (P value < 0.0001) and 2.02-fold (P value = 0.003), respectively. All four transcripts achieved exceptionally high specificity (97.5–100 %) but only moderate sensitivity (29.3–56.1 %) for discrimination of CRC samples from ANTS, reflecting their stringent discrimination of ANTs at the expense of missing a subset of tumors. Taken together, our results revealed a coordinated dysregulation of Wnt-related genes in CRC, i.e. loss of TSPOAP1-AS1 alongside gain of RNF43, TMEM147-AS1, and FOXP4-AS1 expression, highlighting their potential as complementary biomarkers.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100155"},"PeriodicalIF":3.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-26DOI: 10.1016/j.adcanc.2025.100154
Yunfan Wang , Ke Min , Jun Shi , Jun Jin , Qiang Yao , Jianping Zhou , Weimin Wang
Background
Gastric cancer (GC) is a common digestive malignancy with high mortality, primarily due to liver metastasis. The underlying molecular mechanisms driving this process remain poorly understood. This study aimed to identify novel prognostic biomarkers for GC liver metastasis.
Methods
We analyzed mRNA expression data from non-metastatic, liver-metastatic, and other-metastatic GC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was employed to identify key gene modules and hub genes associated with liver metastasis. Potential biomarkers were screened based on differential expression, prognostic value determined by Kaplan-Meier survival analysis, and risk assessment via a univariate Cox regression model. The findings were then validated in an independent cohort of 380 GC patients.
Results
The WGCNA identified a gene module (MEgrey) significantly correlated with GC liver metastasis. Within this module, TMEM119 and NRXN2 were identified as key hub genes whose expression was significantly higher in the liver metastasis group compared to the non-metastatic and other-metastatic groups. High expression of either TMEM119 or NRXN2 was associated with shorter overall survival (OS) and indicated an increased risk of mortality (HR > 1). These findings were confirmed in our validation cohort.
Conclusion
TMEM119 and NRXN2 are promising prognostic biomarkers for predicting liver metastasis in GC patients and may serve as potential therapeutic targets.
{"title":"TMEM119 and NRXN2 as prognostic biomarkers for liver metastasis in gastric cancer","authors":"Yunfan Wang , Ke Min , Jun Shi , Jun Jin , Qiang Yao , Jianping Zhou , Weimin Wang","doi":"10.1016/j.adcanc.2025.100154","DOIUrl":"10.1016/j.adcanc.2025.100154","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is a common digestive malignancy with high mortality, primarily due to liver metastasis. The underlying molecular mechanisms driving this process remain poorly understood. This study aimed to identify novel prognostic biomarkers for GC liver metastasis.</div></div><div><h3>Methods</h3><div>We analyzed mRNA expression data from non-metastatic, liver-metastatic, and other-metastatic GC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was employed to identify key gene modules and hub genes associated with liver metastasis. Potential biomarkers were screened based on differential expression, prognostic value determined by Kaplan-Meier survival analysis, and risk assessment via a univariate Cox regression model. The findings were then validated in an independent cohort of 380 GC patients.</div></div><div><h3>Results</h3><div>The WGCNA identified a gene module (MEgrey) significantly correlated with GC liver metastasis. Within this module, TMEM119 and NRXN2 were identified as key hub genes whose expression was significantly higher in the liver metastasis group compared to the non-metastatic and other-metastatic groups. High expression of either TMEM119 or NRXN2 was associated with shorter overall survival (OS) and indicated an increased risk of mortality (HR > 1). These findings were confirmed in our validation cohort.</div></div><div><h3>Conclusion</h3><div>TMEM119 and NRXN2 are promising prognostic biomarkers for predicting liver metastasis in GC patients and may serve as potential therapeutic targets.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100154"},"PeriodicalIF":3.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vasculogenic Mimicry (VM) is a distinct mode of tumor vascularization, separate from angiogenesis, whereby highly invasive cancer cells form functional vascular-like structures to facilitate the transport of blood and tumor cells. Unlike angiogenesis, which is mediated by endothelial cells, VM is exclusively driven by cancer cells and is recognized as a pivotal mechanism in breast cancer progression. This review is designed to elucidate the cellular and molecular mechanisms underpinning VM in breast cancer metastasis, with emphasis placed on the contributions of the tumor microenvironment, epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs). The involvement of key signaling pathways, such as EphA2/PIK3R1/CTNNB1, is also examined. Furthermore, the role of VM in promoting tumor growth, invasion, and distant metastasis is analyzed, alongside its contribution to resistance against established anti-angiogenic therapies. The therapeutic potential of targeting VM is explored, encompassing the development of specific inhibitors and combination therapy strategies. Additionally, the utility of VM as a prognostic and predictive marker in breast cancer is evaluated, and future research directions, along with challenges in clinical translation, are outlined.
{"title":"The mechanisms of action and targeting potential of vasculogenic mimicry in breast cancer metastasis","authors":"Cangtai Guan, Liangyu Hao, Biyou Gong, Lixiang Zheng","doi":"10.1016/j.adcanc.2025.100153","DOIUrl":"10.1016/j.adcanc.2025.100153","url":null,"abstract":"<div><div>Vasculogenic Mimicry (VM) is a distinct mode of tumor vascularization, separate from angiogenesis, whereby highly invasive cancer cells form functional vascular-like structures to facilitate the transport of blood and tumor cells. Unlike angiogenesis, which is mediated by endothelial cells, VM is exclusively driven by cancer cells and is recognized as a pivotal mechanism in breast cancer progression. This review is designed to elucidate the cellular and molecular mechanisms underpinning VM in breast cancer metastasis, with emphasis placed on the contributions of the tumor microenvironment, epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs). The involvement of key signaling pathways, such as EphA2/PIK3R1/CTNNB1, is also examined. Furthermore, the role of VM in promoting tumor growth, invasion, and distant metastasis is analyzed, alongside its contribution to resistance against established anti-angiogenic therapies. The therapeutic potential of targeting VM is explored, encompassing the development of specific inhibitors and combination therapy strategies. Additionally, the utility of VM as a prognostic and predictive marker in breast cancer is evaluated, and future research directions, along with challenges in clinical translation, are outlined.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100153"},"PeriodicalIF":3.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pseudogenes were historically considered non-functional genomic relics. However, they are now acknowledged as possible regulators in various biological processes, including cancer. In breast cancer, emerging evidence implies the critical roles of pseudogenes in tumorigenesis, progression, and metastasis. These roles are mediated through mechanisms such as competitive endogenous RNA (ceRNA) activity, modulation of gene expression, and interaction with signaling pathways. Some pseudogenes, such as DUXAP8, CYP4Z2P, RPSAP52, POU5F1P1, POU5F1P3, POU5F1P4 and OCT4-PG1 exhibit dysregulated expression in breast cancer tissues, influencing oncogenic or tumor-suppressive pathways. Dysregulation of several pseudogenes has been associated with reduced survival of patients. Additionally, their ability to mimic parental genes or sequester microRNAs highlights their functional significance in disease pathogenesis. Despite challenges in differentiating pseudogenes from their parental genes, advancements in genomic technologies have enabled deeper exploration of their biological roles. This review summarizes current knowledge on pseudogene involvement in breast cancer, emphasizing their potential as biomarkers and therapeutic targets. Further research is needed to fully elucidate their mechanisms and clinical relevance in breast cancer biology.
{"title":"The role of pseudogenes in breast cancer: from non-coding relics to functional regulators","authors":"Parisa Esmaeili Motalgh, Mohsen Ahmadi, Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100152","DOIUrl":"10.1016/j.adcanc.2025.100152","url":null,"abstract":"<div><div>Pseudogenes were historically considered non-functional genomic relics. However, they are now acknowledged as possible regulators in various biological processes, including cancer. In breast cancer, emerging evidence implies the critical roles of pseudogenes in tumorigenesis, progression, and metastasis. These roles are mediated through mechanisms such as competitive endogenous RNA (ceRNA) activity, modulation of gene expression, and interaction with signaling pathways. Some pseudogenes, such as <em>DUXAP8, CYP4Z2P</em>, <em>RPSAP52</em>, <em>POU5F1P1</em>, <em>POU5F1P3</em>, <em>POU5F1P4</em> and <em>OCT4-PG1</em> exhibit dysregulated expression in breast cancer tissues, influencing oncogenic or tumor-suppressive pathways. Dysregulation of several pseudogenes has been associated with reduced survival of patients. Additionally, their ability to mimic parental genes or sequester microRNAs highlights their functional significance in disease pathogenesis. Despite challenges in differentiating pseudogenes from their parental genes, advancements in genomic technologies have enabled deeper exploration of their biological roles. This review summarizes current knowledge on pseudogene involvement in breast cancer, emphasizing their potential as biomarkers and therapeutic targets. Further research is needed to fully elucidate their mechanisms and clinical relevance in breast cancer biology.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100152"},"PeriodicalIF":3.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18DOI: 10.1016/j.adcanc.2025.100151
Andrew M. Lewis Jr. , Gideon Foseh , Keith Peden , Adovi Akue , Mark KuKuruga , Daniel Rotroff , Gladys Lewis , Ilya Mazo
We have investigated the expression of selected genes and miRNAs that have been found to be associated with human cancer-stem cells for their involvement in the neoplastic evolution of our AGMK1-9T7 cell line from a non-tumorigenic status at passage (p)13 to a tumorigenic/metastatic status at p40 to p43. Among these genes are CD90, CD44, CD24, PODXL, ALDH1A, ALDHA2, and ALDHA3 genes, as well as 17 other genes and 38 miRNAs. While CD90 and CD24 were not expressed by any passages of AGMK1-9T7 cells, CD44 was expressed in cells at p13, p23, p33, and p43. The expression of PODXL was first detected as weakly expressed at p33 but was highly expressed by p43. Of the 17 genes that have been associated with human cancer-stem-cell functions that we examined across this spectrum of neoplasia, 5 were up-regulated >2 log2 fold and 8 were down-regulated >2 log2 fold. The expression of the ALDH1A genes, which have been associated with cancer-stem cells, was investigated by the ALDEFLUOR assay in AGMK1-9T7 cells from p13 to p43. Using RT-qPCR, the ALDH1A2 gene was found to be up-regulated in cells from p13 to p43. Twenty-six of the 38 miRNAs reported to be associated with human cancer-stem cells were expressed by the AGMK1-9T7 cells at different passages. From these data, we propose that the AGMK1-9T7 cells are evolving from their non-tumorigenic state to become tumor cells and potentially cancer-stem cells by p43. We suggest that this in vitro system might provide a model to investigate the role of these processes in neoplastic development in humans.
{"title":"Evolution of the AGMK1-9T7 GLI1+ progenitor cells to become tumor cells and potentially cancer-stem cells","authors":"Andrew M. Lewis Jr. , Gideon Foseh , Keith Peden , Adovi Akue , Mark KuKuruga , Daniel Rotroff , Gladys Lewis , Ilya Mazo","doi":"10.1016/j.adcanc.2025.100151","DOIUrl":"10.1016/j.adcanc.2025.100151","url":null,"abstract":"<div><div>We have investigated the expression of selected genes and miRNAs that have been found to be associated with human cancer-stem cells for their involvement in the neoplastic evolution of our AGMK1-9T7 cell line from a non-tumorigenic status at passage (p)13 to a tumorigenic/metastatic status at p40 to p43. Among these genes are CD90, CD44, CD24, PODXL, ALDH1A, ALDHA2, and ALDHA3 genes, as well as 17 other genes and 38 miRNAs. While CD90 and CD24 were not expressed by any passages of AGMK1-9T7 cells, CD44 was expressed in cells at p13, p23, p33, and p43. The expression of PODXL was first detected as weakly expressed at p33 but was highly expressed by p43. Of the 17 genes that have been associated with human cancer-stem-cell functions that we examined across this spectrum of neoplasia, 5 were up-regulated >2 log2 fold and 8 were down-regulated >2 log2 fold. The expression of the ALDH1A genes, which have been associated with cancer-stem cells, was investigated by the ALDEFLUOR assay in AGMK1-9T7 cells from p13 to p43. Using RT-qPCR, the ALDH1A2 gene was found to be up-regulated in cells from p13 to p43. Twenty-six of the 38 miRNAs reported to be associated with human cancer-stem cells were expressed by the AGMK1-9T7 cells at different passages. From these data, we propose that the AGMK1-9T7 cells are evolving from their non-tumorigenic state to become tumor cells and potentially cancer-stem cells by p43. We suggest that this <em>in vitro</em> system might provide a model to investigate the role of these processes in neoplastic development in humans.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100151"},"PeriodicalIF":3.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-19DOI: 10.1016/j.adcanc.2025.100150
Iman Akhlaghipour , Negin Taghehchian , Meysam Moghbeli
Late diagnosis has a key role in therapeutic failure and tumor relapse. Therefore, assessment of the molecular tumor biology can help to introduce novel early diagnostic markers. MicroRNAs (miRNAs) have important roles in regulation of tumor cell proliferation, invasion, drug resistance, and angiogenesis. Due to the high stability of miRNAs in paraffin-embedded tissues and body fluids, they can be also used as the non-invasive markers for cancer screening and early diagnosis. According to numerous reports about the role of miR-103a in various cancers, in the present review we investigated the molecular biology of miR-103a during tumor progression. It has been reported that miR-103a has a dual function as an oncogene and tumor suppressor in various cancers. MiR-103a exerts its role in tumor progression by regulation of signaling pathways, apoptosis, cell cycle, cell metabolism, and transcription factors. This review paves the way in introducing miR-103a as a diagnostic and therapeutic marker among cancer patients following the animal studies and clinical trials.
{"title":"Molecular pathology of microRNA-103a as a probable diagnostic and therapeutic tumor marker","authors":"Iman Akhlaghipour , Negin Taghehchian , Meysam Moghbeli","doi":"10.1016/j.adcanc.2025.100150","DOIUrl":"10.1016/j.adcanc.2025.100150","url":null,"abstract":"<div><div>Late diagnosis has a key role in therapeutic failure and tumor relapse. Therefore, assessment of the molecular tumor biology can help to introduce novel early diagnostic markers. MicroRNAs (miRNAs) have important roles in regulation of tumor cell proliferation, invasion, drug resistance, and angiogenesis. Due to the high stability of miRNAs in paraffin-embedded tissues and body fluids, they can be also used as the non-invasive markers for cancer screening and early diagnosis. According to numerous reports about the role of miR-103a in various cancers, in the present review we investigated the molecular biology of miR-103a during tumor progression. It has been reported that miR-103a has a dual function as an oncogene and tumor suppressor in various cancers. MiR-103a exerts its role in tumor progression by regulation of signaling pathways, apoptosis, cell cycle, cell metabolism, and transcription factors. This review paves the way in introducing miR-103a as a diagnostic and therapeutic marker among cancer patients following the animal studies and clinical trials.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100150"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-14DOI: 10.1016/j.adcanc.2025.100149
Yanfei Cui , Minghua Zhang , Sijia Zhang , Yanli Cai , Yangang Qu , Lihua Luo
Background
Lung cancer often develops resistance to radiotherapy (RT), which undermines its therapeutic efficacy. Disulfiram (DSF), a drug commonly used in the treatment of alcohol use disorders, has shown potential in inducing anti-tumor effects. However, its impact on radioresistance in lung cancer and its effects on the tumor immune microenvironment have not been fully elucidated.
Methods
Clonogenic assays, Rad51 foci formation, and a nude mouse model were employed to assess the impact of DSF on lung cancer radiosensitivity. Immune profiling was conducted using flow cytometry, and downstream mechanisms were investigated using RT-qPCR and Western blotting. The therapeutic effects of the combination of DSF, RT, and anti-PD-L1 antibody were further validated in a C57BL/6 mouse tumor model.
Results
DSF increased radiosensitivity in lung cancer cells, enhanced CD8+ T cell infiltration, and upregulated PD-L1 expression through c-Myc. The combination of DSF, RT, and anti-PD-L1 antibody resulted in the most significant anti-tumor effects.
Conclusions
DSF effectively mitigates radioresistance in lung cancer and enhances the efficacy of radioimmunotherapy, offering a promising therapeutic strategy for improving treatment outcomes.
{"title":"Disulfiram alone regulates the radiosensitivity of lung cancer through NF-κB pathway and regulates the immune microenvironment after radiotherapy by targeting PD-L1 through c-Myc","authors":"Yanfei Cui , Minghua Zhang , Sijia Zhang , Yanli Cai , Yangang Qu , Lihua Luo","doi":"10.1016/j.adcanc.2025.100149","DOIUrl":"10.1016/j.adcanc.2025.100149","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer often develops resistance to radiotherapy (RT), which undermines its therapeutic efficacy. Disulfiram (DSF), a drug commonly used in the treatment of alcohol use disorders, has shown potential in inducing anti-tumor effects. However, its impact on radioresistance in lung cancer and its effects on the tumor immune microenvironment have not been fully elucidated.</div></div><div><h3>Methods</h3><div>Clonogenic assays, Rad51 foci formation, and a nude mouse model were employed to assess the impact of DSF on lung cancer radiosensitivity. Immune profiling was conducted using flow cytometry, and downstream mechanisms were investigated using RT-qPCR and Western blotting. The therapeutic effects of the combination of DSF, RT, and anti-PD-L1 antibody were further validated in a C57BL/6 mouse tumor model.</div></div><div><h3>Results</h3><div>DSF increased radiosensitivity in lung cancer cells, enhanced CD8<sup>+</sup> T cell infiltration, and upregulated PD-L1 expression through c-Myc. The combination of DSF, RT, and anti-PD-L1 antibody resulted in the most significant anti-tumor effects.</div></div><div><h3>Conclusions</h3><div>DSF effectively mitigates radioresistance in lung cancer and enhances the efficacy of radioimmunotherapy, offering a promising therapeutic strategy for improving treatment outcomes.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100149"},"PeriodicalIF":3.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-05DOI: 10.1016/j.adcanc.2025.100148
April Kirkendoll
The emergence of cancer is a multistep process, with passage through a so-called precancerous stage as part of the development. Biopsies of suspicious lesions often reveal cells that are altered or abnormal, and those anomalous cells, while often still benign, indicate local conditions conducive to carcinogenesis. Most of the altered cells never develop into cancers, and it is unknown what may trigger malignancy. This report reexamines existing data to provide insights into the conditions necessary to prime a relatively benign and latent cell with malignant potential to respond to a stimulus and transform into cancer. I propose that normal, well-established reactions to cellular insults over time induce conditions within the affected cell which predispose it to malignant transformation. Then, cumulative, age-related changes in the stromal milieu, from a burgeoning population of senescent cells, inadvertently facilitates the progression of mutant cells, contributing to the increase in late life cancers, via incremental seclusion from normal somatic tissues. Within an increasingly exclusive compartment, cells begin a cycle of crosstalk upon each other, incrementally modifying the isolated population of cells with multiple dynamic morphogen gradients that converge, amplify, and erase epigenetic memory within the innermost cells, reprogramming them to a stem cell-like state, and priming them to transform into a novel tissue.
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Pub Date : 2025-08-02DOI: 10.1016/j.adcanc.2025.100147
Ligang Ma , Ruixin Li , Junjie Su , Qiong Cao , Haojie Wang , Zhihao Wei , Chengliang Wang , Chengdong Zhang , Guanyu Li , Wang Qin , Zheng Zhang , Chu Wang , Yingao Zhu , Jingjing Zhao , Shiyong Xin , Jun Ma
Background
With increasing evidence indicating that immune cells significantly contribute to tumor progression, elucidating their role in tumor prognosis and therapy has become imperative. This study aims to thoroughly characterize tumor-infiltrating immune cells in bladder cancer (BLCA) and identify key immune cells and gene models associated with prognosis and therapeutic outcomes in BLCA.
Methods
Initially, we assessed the relationship between the abundance of infiltrating immune cells and prognosis, CD8+T cell was selected to establish the risk model, which was constructed based on five key genes. Then ROC curve was drawn to demonstrate the risk model had high prognosis predictive value in BLCA.
Results
Our correlation analysis revealed that riskscore was negatively associated with several steps of the tumor immune cycle. Additionally, the risk score exhibited a negative correlation with the expression levels of CD8,CD274,IFNG, Merck18, and several common immune checkpoints. Furthermore, the tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were significantly higher in the high-score group compared to the low-score group. Notably, the risk score demonstrated a negative correlation with the enrichment score of immunotherapy-related pathways, indicating that the therapeutic benefit was greater in the low-score group than in the high-score group. Then, a total of 171 chemotherapy and targeted drugs were identified. Subsequently, immunohistochemistry, EDU and Western blot were used to verify our result.
Conclusions
Our results confirmed that the tumor infiltration CD8+ T cells in tumors plays a critical role in the prognosis and treatment of bladder cancer (BLCA). This insight may offer new directions and inspiration for prognostic prediction and therapeutic strategies for bladder cancer in the future.
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