Tumors have unbounded components fitted which execute widespread pathophysiologies. It has been noted that tumor associated inflammation attributes to metastatic endpoints making it an aggressive phenotype. The inflammatory cells and system are set to have a cross talk with tumor cells in the microenvironment varying with the cancer. Likewise, EMT process might also trigger inflammation by the cancer cells. On the other hand, hybrid EMT possesses characteristics of both epithelial and mesenchymal nature which are said to possess unique stemness and express therapeutic resistance. A deeper understanding of the immune events in the tumor microenvironment is necessary to gain better understanding. Further, interpreting how cancer cells are attuning to stress and harsh environments is instrumental in learning about the concept of hybrid EMT. The current review focusses on the interrelationship between inflammation and how might aid in the hybrid EMT phenotype or the regulatory inflammatory factors bolstering hybrid EMT.
{"title":"Hybrid EMT and inflammation: the deadly alliance","authors":"Rohit Gundamaraju , Vidhya Tangeda , Harshini Raja , Chandrashekar Goud , Hima Sree Buddiraju , Vishnu Pulavarthy","doi":"10.1016/j.adcanc.2025.100160","DOIUrl":"10.1016/j.adcanc.2025.100160","url":null,"abstract":"<div><div>Tumors have unbounded components fitted which execute widespread pathophysiologies. It has been noted that tumor associated inflammation attributes to metastatic endpoints making it an aggressive phenotype. The inflammatory cells and system are set to have a cross talk with tumor cells in the microenvironment varying with the cancer. Likewise, EMT process might also trigger inflammation by the cancer cells. On the other hand, hybrid EMT possesses characteristics of both epithelial and mesenchymal nature which are said to possess unique stemness and express therapeutic resistance. A deeper understanding of the immune events in the tumor microenvironment is necessary to gain better understanding. Further, interpreting how cancer cells are attuning to stress and harsh environments is instrumental in learning about the concept of hybrid EMT. The current review focusses on the interrelationship between inflammation and how might aid in the hybrid EMT phenotype or the regulatory inflammatory factors bolstering hybrid EMT.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100160"},"PeriodicalIF":3.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465150","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}
Long non-coding RNAs (lncRNAs) have important roles in gene regulation and disease pathogenesis. Among them, PTPRG-AS1 (Protein Tyrosine Phosphatase Receptor Type G Antisense RNA 1) has emerged as a potential player in several cancers, particularly breast cancer. This lncRNA has also been found to be over-expressed in nasopharyngeal carcinoma and lung cancer, among other cancers. Moreover, up-regulation of this lncRNA is associated with metastatic potential of gastric cancer, epithelial ovarian cancer, osteosarcoma, hepatocellular carcinoma and triple negative breast cancer. Several microRNAs have been reported as potential interacting molecules with PTPRG-AS1. This article explores the role of PTPRG-AS1 through a literature-based review and bioinformatics analysis, highlighting its molecular mechanisms, expression patterns, and clinical implications. The data summarized in this review may help design of novel anti-cancer therapies, particularly focusing on combating cancer hallmarks, such as stemness and invasion. However, further experimental validation is needed before implementation of these results in the clinical settings.
{"title":"The multifaceted functions of lncRNA PTPRG-AS1 in human cancers: An in-depth investigation through extensive bioinformatic analyses and literature review","authors":"Mohsen Ahmadi , Zahra Tajik , Kiana Salmani , Fatemeh Ghadyani , Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100159","DOIUrl":"10.1016/j.adcanc.2025.100159","url":null,"abstract":"<div><div>Long non-coding RNAs (lncRNAs) have important roles in gene regulation and disease pathogenesis. Among them, PTPRG-AS1 (Protein Tyrosine Phosphatase Receptor Type G Antisense RNA 1) has emerged as a potential player in several cancers, particularly breast cancer. This lncRNA has also been found to be over-expressed in nasopharyngeal carcinoma and lung cancer, among other cancers. Moreover, up-regulation of this lncRNA is associated with metastatic potential of gastric cancer, epithelial ovarian cancer, osteosarcoma, hepatocellular carcinoma and triple negative breast cancer. Several microRNAs have been reported as potential interacting molecules with PTPRG-AS1. This article explores the role of PTPRG-AS1 through a literature-based review and bioinformatics analysis, highlighting its molecular mechanisms, expression patterns, and clinical implications. The data summarized in this review may help design of novel anti-cancer therapies, particularly focusing on combating cancer hallmarks, such as stemness and invasion. However, further experimental validation is needed before implementation of these results in the clinical settings.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100159"},"PeriodicalIF":3.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361056","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 : 2025-10-22DOI: 10.1016/j.adcanc.2025.100157
Maria Dravecka , Claire Wells , Ole Morten Seternes , Jakob Mejlvang
Due to cancer cell metabolism and disorganized tissue structure, the tumour microenvironment is associated with several pathophysiological conditions, including hypoxia, nutrient deprivation, accumulation of waste products, and acidification of the tumour microenvironment (tumour acidosis). Despite the belief that tumour acidosis drives tumorigenesis, it is still unclear how cancer cells respond to acidosis in the absence of other pathophysiological conditions. Here, we investigate how both acute and prolonged acidosis (pH 6.8) affects different epithelial features of a panel of carcinoma cell lines. We find that acute acidosis in all cell lines investigated represses cell growth and causes a disturbance of adherens junctions and apical-basal polarity, reminiscent of epithelial-to-mesenchymal transition (EMT). However, these changes did not coincide with altered expression of E− and N-cadherin. Neither did acute acidosis have a general effect on adhesion and migration in our panel of cell lines. Exposing our panel of carcinoma cell lines to acidosis for more than six weeks did not lead to adaptations restoring cell growth. On the contrary, prolonged acidosis caused one cell line (A431) to halt proliferation. Another cell line (A549) reacted to prolonged acidosis by gradually inducing the expression of ZEB2, which in turn orchestrated cadherin switching, possibly indicating a gradual induction of EMT. In the rest of the cell lines, we did not find any noticeable effect of prolonged acidosis. Lastly, all cell lines quickly restored their original phenotype and growth rate when returned to media with normal pH (pH 7.5). Collectively, our findings reveal that carcinoma cells exposed to moderate acidosis (pH 6.8) generally exhibit slower proliferation rates and a reduction in apical-basal polarity. Furthermore, we conclude that prolonged exposure to acidic conditions, depending on the specific cell line, may elicit responses that could influence tumour progression and the efficacy of cancer treatments.
{"title":"The effect of acute and prolonged acidosis on a panel of carcinoma cell lines","authors":"Maria Dravecka , Claire Wells , Ole Morten Seternes , Jakob Mejlvang","doi":"10.1016/j.adcanc.2025.100157","DOIUrl":"10.1016/j.adcanc.2025.100157","url":null,"abstract":"<div><div>Due to cancer cell metabolism and disorganized tissue structure, the tumour microenvironment is associated with several pathophysiological conditions, including hypoxia, nutrient deprivation, accumulation of waste products, and acidification of the tumour microenvironment (tumour acidosis). Despite the belief that tumour acidosis drives tumorigenesis, it is still unclear how cancer cells respond to acidosis in the absence of other pathophysiological conditions. Here, we investigate how both acute and prolonged acidosis (pH 6.8) affects different epithelial features of a panel of carcinoma cell lines. We find that acute acidosis in all cell lines investigated represses cell growth and causes a disturbance of adherens junctions and apical-basal polarity, reminiscent of epithelial-to-mesenchymal transition (EMT). However, these changes did not coincide with altered expression of E− and N-cadherin. Neither did acute acidosis have a general effect on adhesion and migration in our panel of cell lines. Exposing our panel of carcinoma cell lines to acidosis for more than six weeks did not lead to adaptations restoring cell growth. On the contrary, prolonged acidosis caused one cell line (A431) to halt proliferation. Another cell line (A549) reacted to prolonged acidosis by gradually inducing the expression of ZEB2, which in turn orchestrated cadherin switching, possibly indicating a gradual induction of EMT. In the rest of the cell lines, we did not find any noticeable effect of prolonged acidosis. Lastly, all cell lines quickly restored their original phenotype and growth rate when returned to media with normal pH (pH 7.5). Collectively, our findings reveal that carcinoma cells exposed to moderate acidosis (pH 6.8) generally exhibit slower proliferation rates and a reduction in apical-basal polarity. Furthermore, we conclude that prolonged exposure to acidic conditions, depending on the specific cell line, may elicit responses that could influence tumour progression and the efficacy of cancer treatments.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100157"},"PeriodicalIF":3.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361517","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 : 2025-10-22DOI: 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}
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