{"title":"The role of MICAL2 in cancer progression: mechanisms, challenges, and therapeutic potential.","authors":"Ruiying Wang, Zhijuan Hou, Xiao Gao, Binyan Wu, Huizheng Hu, Hongpei Wu","doi":"10.1007/s13577-025-01212-z","DOIUrl":"https://doi.org/10.1007/s13577-025-01212-z","url":null,"abstract":"<p><p>Cancer is the greatest threat to public health worldwide and a major cause of human death. Compared with conventional chemotherapy, agents targeting key oncogenic drivers and signaling mechanisms are becoming an attractive treatment strategy. Molecule interacting with CasL 2 (MICAL2) is a flavin protein monooxygenase family protein that interacts with CasL2 and is involved in cytoskeletal redox regulation, axon-directed regulation, cell transport, and apoptosis. MICAL2 induces F-actin depolymerization through REDOX modification, thereby promoting the expression of epithelial-mesenchymal transition (EMT)-related proteins and inducing cancer cell invasion and proliferation. Mechanistically, MICAL2 induces EMT by regulating the serum response factor (SRF)/myocardin-related transcription factor A (MRTF-A) signaling pathway, and the semaphorin/plexin pathway and inducing reactive oxygen species (ROS) production. Recent studies have shown that MICAL2 is highly expressed in tumors, accelerates tumor progression, and is a novel tumor-promoting factor. This article summarizes recent research findings to review the biological functions of MICAL2, the potential mechanisms related to cancer progression, and discusses the challenges and prospects in this area, providing a new theoretical basis for clinical molecular targeted therapy for cancer.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"89"},"PeriodicalIF":3.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-04-15DOI: 10.1007/s13577-025-01215-w
Xuelian Liu, Hang Ren, Anjin Wang, Ziyan Liang, Su Min, Shijie Yao, Shimeng Wan, Yang Gao, Hua Wang, Hongbing Cai
{"title":"SIX1 enhances aerobic glycolysis and progression in cervical cancer through ENO1.","authors":"Xuelian Liu, Hang Ren, Anjin Wang, Ziyan Liang, Su Min, Shijie Yao, Shimeng Wan, Yang Gao, Hua Wang, Hongbing Cai","doi":"10.1007/s13577-025-01215-w","DOIUrl":"https://doi.org/10.1007/s13577-025-01215-w","url":null,"abstract":"<p><p>Cervical cancer is a significant threat to women's health, and its incidence in China has been increasing in recent years. Treating advanced and recurrent cervical cancer has become increasingly challenging, highlighting the urgent need to identify new therapeutic targets for this disease. SIX1 is associated with cell proliferation, metastasis, and chemoresistance in various human malignancies. SIX1 overexpression in cervical cancer tissues has been linked to increased clinical stage and lymph node metastasis; however, the regulatory function of SIX1 in cervical cancer remains largely unexplored. In this study, we found that SIX1 promotes cervical cancer cell proliferation, invasion, and migration by enhancing glucose metabolism. Additionally, SIX1 was shown to influence the glycolytic process in cervical cancer by upregulating GLUT1, PFK1, PGK1, ENO1, and PKM2 expression. Furthermore, we identified a binding site for SIX1 in the ENO1 promoter region, demonstrating that SIX1 has a regulatory effect. These results suggest that SIX1 regulates proliferation and glucose metabolism in cervical cancer cells by promoting the transcription of key glycolytic enzymes, such as ENO1. Understanding this regulatory mechanism is crucial for identifying potential therapeutic targets for cervical cancer.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"88"},"PeriodicalIF":3.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RFX5 promotes the progression of triple-negative breast cancer through transcriptional activation of JAG1.","authors":"Chenhao Li, Xin Wang, Dongliang Shi, Meng Yang, Wenhua Yang, Liang Chen","doi":"10.1007/s13577-025-01216-9","DOIUrl":"https://doi.org/10.1007/s13577-025-01216-9","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by high recurrence rates, low survival rates, and a lack of therapeutic targets. Regulatory Factor X5 (RFX5) is a critical transcription factor during tumor progression. However, the role of RFX5 involving breast cancer or TNBC has not been studied. This study obtained 60 tumor samples of TNBC for analysis and ascertained that RFX5 is linked with the severe stage. We constructed RFX5 knockdown and overexpression models involving TNBC cells. RFX5 overexpression enhanced TNBC cell proliferation by detecting cell vitality and replication of DNA and analyzing cell cycle data. RFX5 facilitated cell migration and invasion, which were determined by wound healing and Transwell assays. The anti-apoptotic RFX5 properties were confirmed with Hoechst staining and Annexin V/PI apoptosis assays. The Notch pathway was activated in TNBC, and Jagged canonical Notch ligand 1 (JAG1) could enhance TNBC growth and metastasis. RFX5 upregulation elevated JAG1 mRNA and protein levels. Chromatin immunoprecipitation and luciferase reporter assays indicated that RFX5 promoted the transcriptional activation of JAG1 by binding the promoter (- 1890/+ 15 or - 1359/+ 15 area). JAG1 knockdown reduced RFX5-induced expression of Notch signaling-related factors Notch1, NICD, and Hes1. This paper indicated that RFX5 is a transcription factor for JAG1 and established that RFX5 could activate the Notch pathway via transcriptional activation of JAG1 and promote TNBC progression. Targeting RFX5 could be a promising therapeutic approach against TNBC.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"86"},"PeriodicalIF":3.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-04-12DOI: 10.1007/s13577-025-01210-1
José-Luis Carrasco-Juan, Olga Tapia, Miriam González-Gómez, Abian Vega-Falcón, Sonia García-Hernández, Alexis Rufino-Gómez, Rafael Méndez-Medina, Hugo Álvarez-Arguelles Cabrera
{"title":"Ovarian Leydig cells and neural crests.","authors":"José-Luis Carrasco-Juan, Olga Tapia, Miriam González-Gómez, Abian Vega-Falcón, Sonia García-Hernández, Alexis Rufino-Gómez, Rafael Méndez-Medina, Hugo Álvarez-Arguelles Cabrera","doi":"10.1007/s13577-025-01210-1","DOIUrl":"https://doi.org/10.1007/s13577-025-01210-1","url":null,"abstract":"<p><p>In our search for markers to identify and study ovarian Leydig cells, we utilized immunohistochemical techniques and visualized the results using conventional and confocal microscopy. We successfully employed steroidogenic factor- 1 (SF1), androgen receptor (AR), and class III β-tubulin as markers. SF1 and AR specifically highlighted the intraneural cell precursors of Leydig cells, which were previously identified in a published case of mature cystic teratoma of the ovary, and the adult ovarian Leydig cells. Furthermore, the transient expression of class III β-tubulin could be associated with the intraneural displacement of these precursors, cooperating in their migration to colonize the ovaries of adult women.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"85"},"PeriodicalIF":3.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-04-12DOI: 10.1007/s13577-025-01213-y
Seyed Mehdi Hoseini, Fateme Montazeri
{"title":"The influence of cell source on the senescence of human mesenchymal stem/stromal cells.","authors":"Seyed Mehdi Hoseini, Fateme Montazeri","doi":"10.1007/s13577-025-01213-y","DOIUrl":"https://doi.org/10.1007/s13577-025-01213-y","url":null,"abstract":"<p><p>While mesenchymal stem/stromal cells (MSCs) exhibit the ability to self-renew, they are not immortal; they eventually reach a point of irreversible growth cessation and functional deterioration following a limited series of population doublings, referred to as replicative senescence. When evaluated according to the criteria set by the International Society for Cell Therapy (ISCT), MSCs show significant differences in their senescence patterns and other characteristics related to their phenotype and function. These differences are attributed to the source of the MSCs and the conditions in which they are grown. MSCs derived from fetal or adult sources have variations in their genome stability, as well as in the expression and epigenetic profile of the cells, which in turn affects their secretome. Understanding the key factors of MSC senescence based on cell source can help to develop effective strategies for regulating senescence and improving the therapeutic potential.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"87"},"PeriodicalIF":3.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vitro properties of four benign meningioma cells derived from WHO grade 1 meningiomas.","authors":"Thanawat Trasaktaweesakul, Pundit Asavaritikrai, Krajang Talabnin, Dusit Kongnawakul, Sukanya Tastub, Pitchanun Jaturutthaweechot, Nopporn Naewwan, Chutima Talabnin","doi":"10.1007/s13577-025-01211-0","DOIUrl":"https://doi.org/10.1007/s13577-025-01211-0","url":null,"abstract":"<p><p>Meningiomas are common intracranial tumors arising from the meninges. They exhibit heterogeneity in their biological behaviors and clinical outcomes. Understanding the molecular mechanisms of meningioma development and progression using in vitro systems is essential for improved diagnosis and targeted therapeutic strategies. In this study, four primary meningioma cells designated as SUT-MG9, SUT-MG12, SUT-MG14, and SUT-MG16 were established from WHO grade 1 meningioma tissues via a primary cell culture technique. The phenotypic and genetic characteristics of the four primary meningioma cells were determined. Four primary meningioma cells presented a spindle-shaped morphology with large nuclei and showed prominent expression of meningioma markers, including somatostatin receptor 2 A and vimentin. Growth characteristics demonstrated that SUT-MG9, SUT-MG12, and SUT-MG14 were fast growing, whereas SUT-MG16 was slow growing. Additionally, the expression levels of relevant genes in cell stemness (SOX2, Nanog, and BMI1) and cell cycle (CDK4, CCND1, and CCNB1) were detected only in SUT-MG12 and SUT-MG14. Interestingly, chemosensitivity assay showed that primary benign meningioma cells were less sensitive to gemcitabine and 5-fluorouracil. Moreover, biochemical profiles revealed high lipid and ester contents, but low nucleic acid contents in all primary meningioma cells compared to malignant meningioma cell lines. In conclusion, the four primary meningioma cells can serve as cell models for further meningioma development and drug treatment studies.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"84"},"PeriodicalIF":3.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-04-09DOI: 10.1007/s13577-025-01218-7
Shuwen Zhang, Xin Lan, Ling Lei
{"title":"LINC01559: roles, mechanisms, and clinical implications in human cancers.","authors":"Shuwen Zhang, Xin Lan, Ling Lei","doi":"10.1007/s13577-025-01218-7","DOIUrl":"https://doi.org/10.1007/s13577-025-01218-7","url":null,"abstract":"<p><p>Long intergenic non-protein coding RNA 1559 (LINC01559), a long non-coding RNA (lncRNA) located on chromosome 12p13.1, plays a critical role in the progression of various cancers. The aberrant expression of LINC01559 significantly impacts multiple biological processes in tumor cells, including cell proliferation, epithelial-mesenchymal transition (EMT), migration, invasion, angiogenesis, and cellular stemness. Notably, the expression levels of LINC01559 correlate with the pathological features and prognosis of several cancers, such as pancreatic, breast, and gastric cancers, and it may serve as a diagnostic marker for non-small cell lung cancer. Moreover, the expression of LINC01559 is regulated by various mechanisms and can influence cancer initiation and progression through a competing endogenous RNA (ceRNA) network, where it interacts with a cohort of eight different microRNAs (miRNAs). Additionally, LINC01559 may directly interact with downstream proteins, thereby promoting their functions or enhancing their stability. LINC01559 is also implicated in key signaling pathways associated with cancer development, including the PI3 K/AKT, RAS, and autophagy signaling pathways. Furthermore, it has been linked to drug resistance in breast cancer and hepatocellular carcinoma. This review provides a comprehensive assessment of the clinical implications of dysregulated LINC01559 expression across various cancer types, highlighting its crucial functions and underlying molecular mechanisms in tumorigenesis. Additionally, we present in-depth discussions and propose hypotheses regarding the functional roles of LINC01559 in cancer pathogenesis, while outlining potential research avenues for future exploration of this molecular target.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"83"},"PeriodicalIF":3.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and characterization of novel cancer cachexia-inducing cell line, Aku60GC, of scirrhous gastric cancer.","authors":"Rei Noguchi, Kazuyoshi Yanagihara, Yuki Iino, Teruo Komatsu, Takanori Kubo, Takuya Ono, Julia Osaki, Yuki Adachi, Shuhei Iwata, Yomogi Shiota, Toshio Seyama, Tadashi Kondo","doi":"10.1007/s13577-025-01208-9","DOIUrl":"10.1007/s13577-025-01208-9","url":null,"abstract":"<p><p>Cancer cachexia is a pathological state characterized by severe weight loss, skeletal muscle depletion, and adipose tissue reduction. Cancer cachexia is observed in gastric cancer (GC) with a higher incidence over 80%. Approximately 80% patients with advanced GC including scirrhous gastric cancer (SGC), which has the worst prognosis among all GC, are affected with cachexia. The exact pathophysiology in SGC cancer cachexia remains elusive, and therapeutic approaches for the cancer cachexia have not been established. Patient-derived cancer cachexia models are promising for elucidating the underlying mechanisms of disease progression and developing novel treatments, none of which originate from SGC. Therefore, we established a novel cancer cachexia-inducing cell line, designated Aku60GC, through stepwise selection of a patient-derived SGC cell line, HSC-60. Subcutaneous implantation of the Aku60GC cells into nude mice resulted in weight loss, muscle atrophy, and adipose tissue depletion with high reproducibility, accompanied by elevation of the circulating cytokines IL-8 and IL-18. Compared to parental HSC-60 cells, Aku60GC cells exhibited additional genomic changes, such as AKT2 and CCNE1 gains, a somatic mutation of RUNX1, and accelerated growth. Thus, our results demonstrate that the Aku60GC cell line is a valuable resource for research on cancer cachexia in SGC.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"82"},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and characterization of NCC-OS2-C1: a novel patient-derived cell line of osteosarcoma.","authors":"Shuhei Iwata, Rei Noguchi, Julia Osaki, Yuki Adachi, Yomogi Shiota, Koichi Ogura, Shogo Nishino, Akihiko Yoshida, Seiji Ohtori, Akira Kawai, Tadashi Kondo","doi":"10.1007/s13577-025-01198-8","DOIUrl":"10.1007/s13577-025-01198-8","url":null,"abstract":"<p><p>Osteosarcoma is the most common primary bone sarcoma with a bimodal age distribution. Complete surgical resection with neoadjuvant chemotherapy is the standard curative treatment, and no effective therapeutic strategy has been established for metastatic cases, resulting in poor prognosis. Osteosarcoma presents complex and heterogeneous clinical and molecular features, and no molecular-targeted drugs are available. Therefore, effective multidisciplinary treatment strategies are urgently required. Patient-derived cell lines are essential tools in basic and translational oncology. Considering the heterogeneity of the disease, we established a novel cell line, NCC-OS2-C1, using surgically resected tumor tissues from a patient with osteosarcoma. NCC-OS2-C1 cells demonstrated constant proliferation, spheroid formation, and invasion. In addition, we demonstrated that NCC-OS2-C1 is applicable for the high-throughput screening of drugs. Thus, NCC-OS2-C1 is a valuable tool for basic and translational research on osteosarcoma.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"81"},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-03-31DOI: 10.1007/s13577-025-01196-w
Deirdre Duff, Siobhan Gargan, Aideen Long
{"title":"Non-muscle myosin heavy chain IIA regulates cell morphology, stress fibre structure, and cell migration in FLO-1 oesophageal adenocarcinoma cells.","authors":"Deirdre Duff, Siobhan Gargan, Aideen Long","doi":"10.1007/s13577-025-01196-w","DOIUrl":"10.1007/s13577-025-01196-w","url":null,"abstract":"<p><p>The incidence of oesophageal adenocarcinoma (OAC) is increasing at a rapid rate in Western countries. Early oesophageal cancer is often asymptomatic and metastatic disease is common at presentation leading to poor prognosis and survival rates. Cell migration is tightly controlled in the healthy cell but can become dysregulated in diseases such as OAC where increased cell motility and migration can contribute to metastasis. We investigated the role of an actin-based molecular motor, non-muscle myosin heavy chain IIA (NMHCIIA) in the migratory capacity of oesophageal adenocarcinoma cells. Immunofluorescence microscopy and ratiometric imaging demonstrated that NMHCIIA co-localises with F-actin at the leading edge and retracting rear of migrating FLO-1 OAC cells. siRNA-mediated depletion of NMHCIIA from FLO-1 cells altered cell morphology, gave rise to an increased number of stress fibre like structures and reduced FLO-1 cell migration. These findings suggest that NMHCIIA influences FLO-1 cell migration by regulating F-actin dynamics and the actin cytoskeleton, providing insight into the mechanisms of migration employed by OAC cells and identifying NMHCIIA as a potential therapeutic target for this disease.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"80"},"PeriodicalIF":3.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}