Pathology, research and practice最新文献

{"title":"GSTM1 and GSTT1 deletions in penile cancer are associated with TNM stage but not with HPV DNA status","authors":"Ana Paula Abreu ,&nbsp;Jhessica Gomes ,&nbsp;Jucileide Mota ,&nbsp;Ana Paula Almeida ,&nbsp;Rita Carvalhal ,&nbsp;Flávia Vidal ,&nbsp;Rui Medeiros ,&nbsp;Hugo Sousa ,&nbsp;Melaine Lawall ,&nbsp;Rui M. Gil da Costa ,&nbsp;Haissa O. Brito ,&nbsp;Luciane M.O. Brito","doi":"10.1016/j.prp.2024.155686","DOIUrl":"10.1016/j.prp.2024.155686","url":null,"abstract":"<div><div>Deletions of the <em>GSTT1</em> and <em>GSTM1</em> are associated with chemical carcinogenesis and genitourinary malignancies like bladder cancer, where they correlate with increased tumor aggressiveness. In uterine cervical lesions, <em>GSTT1</em> and <em>GSTM1</em> deletions have also been suggested to facilitate the persistence of human papillomavirus (HPV) infection and HPV-induced carcinogenesis. This work addresses the hypothesis that <em>GSTT1</em>/<em>GSTM1</em> deletions are associated with presence of HPV DNA and aggressiveness in penile cancer, a rare malignancy with HPV+ and HPV- subtypes. Tumor DNA samples and medical records from HPV+ and HPV- penile cancer patients were analyzed. Each sample was screened for <em>GSTT1</em> and <em>GSTM1</em> deletions and for the presence of HPV DNA using PCR-based techniques. 74.5 % of samples contained HPV DNA. 61.8 % of cases showed T2 and T3 staging. There were no differences in the frequencies of <em>GSTT1/GSTM1</em> genotypes between HPV+ and HPV- cases (<em>p</em>&gt;0.05). <em>GSTT1</em>^wt/<em>GSTM</em>^{<em>null</em>} patients were more likely to have higher TNM stages compared with other genotypes (<em>p</em>=0.012), but no differences were observed concerning perineural invasion nor lymphovascular invasion. These findings indicate that <em>GSTT1</em> and <em>GSTM1</em> deletions are common in HPV+ and HPV- penile cancers. <em>GSTM1</em> deletions in the presence of wild-type <em>GSTT1</em> seems to be associated with tumor progression, and additional studies are warranted to confirm its potential as a prognostic marker in penile cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular responses to neoadjuvant FOLFOX6-bevacizumab treatment in colorectal cancers analyzed by single-cell transcriptome analysis","authors":"Sun Shin ,&nbsp;Hyun Ho Kim ,&nbsp;Jae Woong Kim ,&nbsp;Doeun Rim ,&nbsp;Changhyeok An ,&nbsp;Yeun-Jun Chung ,&nbsp;Sug Hyung Lee","doi":"10.1016/j.prp.2024.155681","DOIUrl":"10.1016/j.prp.2024.155681","url":null,"abstract":"<div><div>Neoadjuvant chemotherapy combined with bevacizumab is used to treat colorectal cancer (CRC) patients by targeting tumor and vascular cells. However, it is known that other cells in the tumor microenvironment (TME) also change in response to this treatment. To investigate the changes in TME subpopulations in response to neoadjuvant FOLFOX6 plus bevacizumab, we studied pre- and post-treatment CRC tissues in four patients using single-cell RNA sequencing (scRNA-seq). This analysis classified nine cell types, including epithelial, vascular, immune cells, and fibroblasts. The cellular responses were widespread across the cell types, but there were specific subpopulations that altered, especially in vascular, immune, and fibroblast cells. In vascular subpopulations, CDH13-endothelial, arteriole, and CA4 capillary cells were selectively reduced. In immune cells, CD4+, CD8+ T cells, conventional dendritic cell type 1 (cDC1), and <em>CCL19</em>-expressing migrating DC (migDC-1) increased, while Th17, Th22, and tumor-associated macrophage (TAM) cells decreased, indicating that the treatment might be immunostimulatory. In fibroblasts, two major cancer-associated fibroblasts (matrix CAF (mCAF) and inflammatory CAF (iCAF)) increased, while conventional fibroblasts decreased, suggesting that the treatment remodeled the reparative/inflammatory processes, which might lead to reduced aggressiveness from the cancer-associated fibroblasts. In summary, our study reveals that neoadjuvant FOLFOX6 plus bevacizumab leads to alterations in particular subpopulations of vascular, immune, and reparative/inflammatory cells in the TME of CRCs. These alterations include vascular reduction, immunologic stimulation, and reduction of cancer-associated fibroblasts, which may underlie the responsiveness to the therapy in CRC. Our results may provide insights into the mechanisms of responsiveness/resistance to neoadjuvant FOLFOX6 plus bevacizumab therapy in CRCs.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCL-2 and γ-H2AX immunostaining profile in urothelial bladder cancer prognosis","authors":"Julia Ayumi Ikeda Kawasaki ,&nbsp;Lais Capelasso Lucas Pinheiro ,&nbsp;Isabely Mayara da Silva ,&nbsp;Carlos Alberto Miqueloto ,&nbsp;Karen Brajão de Oliveira ,&nbsp;Diego Luís Ribeiro ,&nbsp;Alda Fiorina Maria Losi Guembarovski ,&nbsp;Fernando Terziotti ,&nbsp;Wilner Martinez-López ,&nbsp;Juliana Mara Serpeloni ,&nbsp;Roberta Losi Guembarovski","doi":"10.1016/j.prp.2024.155680","DOIUrl":"10.1016/j.prp.2024.155680","url":null,"abstract":"<div><div>Urothelial bladder carcinoma (UBC) is a malignant neoplasm of the urinary tract that is highly prevalent worldwide and has a high rate of tumor recurrence. It is known that the <em>BCL2 apoptosis regulator (BCL-2)</em> gene encodes a mitochondrial protein that regulates programmed death cells by apoptosis. In contrast, the <em>H2A.X histone variant</em> (<em>H2AX)</em> gene encodes a histone responsible for regulating and signaling genomic instability processes. The present study aimed to analyze the immunostaining profiles of BCL-2 and γ-H2AX proteins in tissue samples (n=80) from UBC patients (muscle-invasive MI; and non-muscle invasive NMI) using indirect immunohistochemistry and to correlate the results with prognostic and clinical parameters. BCL-2 protein expression was cytoplasmic and absent in half of the samples, including the MI and NMI groups. Strong nuclear expression was observed for γ-H2AX, predominant in the MI samples. The immunostaining profile of both proteins was not associated with tumor recurrence or invasion, and no significant associations were found in relation to prognosis (tumor grade, pathological staging). No significant correlation was found between protein profiles in malignant tissue. All in all, BCL-2 and γ-H2AX did not prove to be candidate markers for UBC clinical management in the present sample, despite their expression in malignant bladder tissue.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal microRNAs in cancer metastasis: A bridge between tumor micro and macroenvironment","authors":"Mohamed J. Saadh ,&nbsp;Amirmohammad Khalifehsoltani ,&nbsp;Abbas Hameed Abdul Hussein ,&nbsp;Omer Qutaiba B. Allela ,&nbsp;Hayder Naji Sameer ,&nbsp;Jasur Rizaev ,&nbsp;Huda Ghassan Hameed ,&nbsp;Ameer Hassan Idan ,&nbsp;Fahad Alsaikhan","doi":"10.1016/j.prp.2024.155666","DOIUrl":"10.1016/j.prp.2024.155666","url":null,"abstract":"<div><div>Malignant tumors are complicated structures of cancer cells that are constantly in communication with their local and distant environment. Exosomes are released by tumor cells and can facilitate the cell-cell interaction within the local microenvironment and the primary tumor. In fact, exosomes are secreted by both tumor and non-tumor cells, to provide a mutual communication network between cells and their micro- and/or macro-environments. Exososmes can contain a variety of biological cargos mostly based on their originated cells. Uptake of these exosomes by their recipient cells results in the alterations that their cargo can exert. MicroRNAs are identified as one of the most critical exosomal components, considering their pivotal regulatory roles in distinct biological process, including metastasis. Release and absorbance of exosomal microRNAs is possible by various cells within the host, and can have distinct biological consequences. Therefore, in this review we will discuss the role of exosomal microRNAs derived from tumor cells and untransformed cells within their micro- and macroenvironment in cancer progression and metastasis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_0060927 promotes colorectal cancer development by sponging miR-331-3p and upregulating TBX2","authors":"Dian Yin,&nbsp;XiaoLu Zhai,&nbsp;Xiu Feng,&nbsp;Mei Hua,&nbsp;Jing Liu,&nbsp;Ying Chen","doi":"10.1016/j.prp.2024.155673","DOIUrl":"10.1016/j.prp.2024.155673","url":null,"abstract":"<div><h3>Background</h3><div>The dysregulation of circular RNAs (circRNAs) is closely associated with the pathogenesis of colorectal cancer (CRC). The present study aimed to elucidate the biological function and mechanism of circ_0060927 in CRC.</div></div><div><h3>Methods</h3><div>5-ethynyl-2’-deoxyuridine, Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, as well as Xenograft tumor models were adopted for in vitro and in vivo analyses. The interaction between microRNA-331–3p (miR-331–3p) and circ_0060927 or T-box transcription factor 2 (TBX2) was verified by the dual-luciferase reporter and RNA pull-down assays.</div></div><div><h3>Results</h3><div>Circ_0060927 deficiency inhibited cell proliferation, autophagy, migration, and invasion and increased cell apoptosis and necrosis in CRC cells, as well as inhibited tumor growth <em>in vivo</em>. Circ_0060927 could bind to miR-331–3p, and circ_0060927 regulated CRC cell behaviors via sponging miR-331–3p. TBX2 was targeted by miR-331–3p, and miR-331–3p targeted TBX2 to exert the anti-cancer role in CRC cells. Mechanically, circ_0060927 regulated TBX2 expression by sequestering miR-331–3p in CRC cells.</div></div><div><h3>Conclusion</h3><div>Circ_0060927 downregulation inhibited CRC progression by regulating the miR-331–3p/TBX2 axis, which might offer a potential treatment target for CRC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of artificial intelligence in neuropathology: Where are we and where do we want to go?","authors":"Giuseppe Broggi ,&nbsp;Manuel Mazzucchelli ,&nbsp;Serena Salzano ,&nbsp;Giuseppe Maria Vincenzo Barbagallo ,&nbsp;Francesco Certo ,&nbsp;Magda Zanelli ,&nbsp;Andrea Palicelli ,&nbsp;Maurizio Zizzo ,&nbsp;Nektarios Koufopoulos ,&nbsp;Gaetano Magro ,&nbsp;Rosario Caltabiano","doi":"10.1016/j.prp.2024.155671","DOIUrl":"10.1016/j.prp.2024.155671","url":null,"abstract":"<div><div>The field of neuropathology, a subspecialty of pathology which studies the diseases affecting the nervous system, is experiencing significant changes due to advancements in artificial intelligence (AI). Traditionally reliant on histological methods and clinical correlations, neuropathology is now experiencing a revolution due to the development of AI technologies like machine learning (ML) and deep learning (DL). These technologies enhance diagnostic accuracy, optimize workflows, and enable personalized treatment strategies. AI algorithms excel at analyzing histopathological images, often revealing subtle morphological changes missed by conventional methods. For example, deep learning models applied to digital pathology can effectively differentiate tumor grades and detect rare pathologies, leading to earlier and more precise diagnoses. Progress in neuroimaging is another helpful tool of AI, as enhanced analysis of MRI and CT scans supports early detection of neurodegenerative diseases. By identifying biomarkers and progression patterns, AI aids in timely therapeutic interventions, potentially slowing disease progression. In molecular pathology, AI’s ability to analyze complex genomic data helps uncover the genetic and molecular basis of neuropathological conditions, facilitating personalized treatment plans. AI-driven automation streamlines routine diagnostic tasks, allowing pathologists to focus on complex cases, especially in settings with limited resources. This review explores AI's integration into neuropathology, highlighting its current applications, benefits, challenges, and future directions.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of doxorubicin by Fe3O4 nanoparticles, reduces multidrug resistance gene expression in ovarian cancer cells","authors":"Roghiyeh Pashaei-Asl ,&nbsp;Soheila Motaali ,&nbsp;Esmaeil Ebrahimie ,&nbsp;Manijeh Mohammadi-Dehcheshmeh ,&nbsp;Mansour Ebrahimi ,&nbsp;Maryam Pashaiasl","doi":"10.1016/j.prp.2024.155667","DOIUrl":"10.1016/j.prp.2024.155667","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer is one of the most common malignancy in women with significant mortality rate due to the resistance to chemotherapy drugs. Doxorubicin (DOX) is a chemotropic agent in ovarian cancer treatment. Overexpression of multidrug resistance (MDR) genes, such as <em>ABCB1</em>, in cancer cells after chemotherapy is one of main problems in clinical applications. Here we have compared the efficiency of doxorubicin-loaded (NIPAAM-DMAEMA) Fe₃O₄ nanocomposite (DOX-NANO) against DOX on <em>ABCB1(</em>MDR1) gene expression in the ovarian cancer cell line.</div></div><div><h3>Materials and methods</h3><div>The cell viability of SKOV-3 cells were evaluated by MTT assay. Real Time PCR was used to measure the expression level of MDR1. MTT data were normalized in 10 different attribute weighting models, also to reveal the interaction between DOX, <em>ABCB1</em>, and ovarian cancer genes, Pathway Studio Database (Elsevier) was used.</div></div><div><h3>Results</h3><div>Cell viability of SKOV-3cells was significantly decreased after 24, 48 and 72 hours (P &lt; 0.0001) of either DOX with IC50 22.38, 0.61 and 0.072 µg/ml or DOX-NANO treatment with IC50 11.54, 1.01, 0.0126 µg/ ml respectively. treatment. Notable decrease in the expression of MDR gene, <em>ABCB1</em>, was observed 48 hours after treatment with DOX-NANO (P &lt; 0.0001) with 26 % in the assessed with control group. Meta-analysis showed the concentration of 10 μg/ml variables was the second most significant feature, whereas the concentration of 0.01 μg/ml recognized the lowest weights. Also, <em>LGALS3</em> is an extra cellular receptor with upregulation in ovarian cancer that interacts with <em>ABCB1</em>.</div></div><div><h3>Conclusion</h3><div>Our findings highlight the beneficial effects of DOX delivery in ovarian cancer cells by nanocomposite as efficient drug delivery method. DOX-NANO is a promising therapeutic reagent to overcome chemotherapy resistance in ovarian cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leukemic B cells expression of CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) in Chronic Lymphocytic Leukemia patients in relation to Treg frequency","authors":"Reham Hammad ,&nbsp;Eman Z. Kandeel ,&nbsp;Claude Lambert ,&nbsp;Ulrich Sack ,&nbsp;Sandy Kujumdshiev ,&nbsp;Arwa Kamhawy ,&nbsp;Omaima I. Abo-Elkheir ,&nbsp;Fatma EL-Zahraa Abd El Hakam ,&nbsp;Alya Mashaal ,&nbsp;Mohammed Ramadan ,&nbsp;Abdel-Aziz A. Zidan ,&nbsp;Nadia M. Hamdy","doi":"10.1016/j.prp.2024.155669","DOIUrl":"10.1016/j.prp.2024.155669","url":null,"abstract":"<div><h3>Background</h3><div>Chronic lymphocytic leukemia (CLL) is characterized by a wide range of tumor-induced immune alterations. Regulatory T cells (Treg) play a central role in these immune responses. CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) are inhibitory markers said to be involved in Treg immune response. We aimed to analyze the expression of CD200 and LAIR-1 on leukemic cells and assess their interactions with the Treg frequency to elucidate their role in the CLL course.</div></div><div><h3>Subjects and methods</h3><div>This study was conducted on 70 participants: 50 newly diagnosed CLL cases classified according to Rai staging system into group 1 (n = 25) patients with stages 0, I, and II, and group 2 (n = 25) of advanced patients with stages III and IV. In addition to control group (n = 20) of healthy adults. Flow cytometry was used to investigate Treg frequency in bone marrow (BM) proportional to CD4+ T cell and to assess leukemic cell expression of CD200 and LAIR-1. Also, <em>in-silico</em> database analysis was performed to identify study markers interactions for future personalized target therapy.</div></div><div><h3>Results</h3><div>Comparison between CLL groups 1 and 2 revealed increased leukemic cell percentage expressing LAIR-1 (<em>p</em> = 0.021) in group 1. Group 2 showed significant increase in frequency of Treg in BM and leukemic cells expressing CD200. There was a strong positive correlation between frequency of Treg and leukemic cells expressing CD200 (r = 0.669, <em>p</em> = 0.000). On the other hand, there was a negative correlation between frequency of Treg and leukemic cell expressing LAIR-1 (r = −0.342, <em>p</em> = 0.015). ROC curve analysis revealed that increased frequency of leukemic cells expressing CD200 yielded sensitivity (SN) and specificity (SP) of 96 % and 84 %, respectively in detecting CLL progression, with an AUC of 0.965. Leukemic cell percentages expressing LAIR-1 yielded a lower SN (75 %), SP (72 %), with an AUC of 0.688.</div></div><div><h3>Conclusion</h3><div>Treg frequency in BM was significantly increased in CLL advanced stages according to Rai classification. Leukemic cells CD200 and LAIR-1 expression were differently associated with Treg frequency. Increased CD200 expressions on leukemic cells can be considered a sensitive and specific biomarker in detecting CLL progression. As demonstrated by the <em>in-silico</em> research, CD200 blockade targeting may offer therapeutic benefits for CLL treatment through Treg suppression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-induced lncARSR aggravates neuroblastoma tumorigenic properties through stabilizing PHOX2B","authors":"Xiangyi Meng ,&nbsp;Zhu Tan ,&nbsp;Bihua Qiu ,&nbsp;Jie Zhang ,&nbsp;Ruobing Wang ,&nbsp;Wensi Ni ,&nbsp;Jialing Fan","doi":"10.1016/j.prp.2024.155670","DOIUrl":"10.1016/j.prp.2024.155670","url":null,"abstract":"<div><div>Neuroblastoma (NB), the most common extracranial solid tumor in pediatric patients, manifests with considerable variability across multiple primary sites. Despite this, the extent of genetic heterogeneity within these tumor foci and the identification of consistent oncogenic drivers remains largely unexplored. Of particular interest, genetic mutations in PHOX2B have been linked to familial cases of NB, yet the underlying molecular mechanisms are not fully delineated. In our research, we focus on unraveling the role of a novel functional long non-coding RNA (lncRNA) associated with PHOX2B in the context of NB. Using NB cell models with overexpressed PHOX2B, combined with lncRNA microarray analysis, we discovered that lncARSR is significantly upregulated in response to PHOX2B overexpression. Subsequent biological assays demonstrated that lncARSR promotes both the proliferation and metastasis of NB cells. Further molecular investigations revealed that lncARSR plays a crucial role in stabilizing PHOX2B expression within NB cells. Moreover, we identified that the expression of lncARSR is regulated by methylation through methyltransferase-like 3 (METTL3), which itself is positively correlated with PHOX2B expression. Rescue experiments underscored the functional importance of METTL3, lncARSR, and PHOX2B in NB cells. In summary, our findings provide new insights into the molecular functions of PHOX2B in the progression of neuroblastoma and propose a novel therapeutic target for this aggressive malignancy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico analysis and comprehensive review of circular-RNA regulatory roles in breast diseases; a step-toward non-coding RNA precision","authors":"Nadia M. Hamdy ,&nbsp;Mona G. El-Sisi ,&nbsp;Sherine M. Ibrahim ,&nbsp;Heba ElNokoudy ,&nbsp;Ahmad A. Hady ,&nbsp;Gamal Eldein Fathy Abd-ellatef ,&nbsp;Al-Aliaa M. Sallam ,&nbsp;Bassant Mohamed Barakat","doi":"10.1016/j.prp.2024.155651","DOIUrl":"10.1016/j.prp.2024.155651","url":null,"abstract":"<div><div>In the current comprehensive review, we first highlighted circRNAs, which are key ncRNAs. Next, we discussed the relationships among circRNAs and breast cancer subtypes via <em>in silico</em> databases analysis and extensive literature search. CircRNAs, that sponge miRNA axes or act as silencers of oncogenic mRNAs, have been extensively addressed in the context of this review. During BC pathogenesis, the circRNA/microRNA/messenger RNA (mRNA) axis plays a major role in disease growth, progression, and survival/resistance and could be targeted for improved treatment options. This review also aimed to address oncogenic and tumor suppressor mRNAs, which are regulated by various circRNAs in BC. Moreover, we mentioned the relation of different circRNAs with cancer hallmarks, patient survival together with drug resistance. Additionally, we discussed circRNAs as vaccines and biomarkers in BC. Finally, we studied exosomal circRNAs as a hot interesting area in the research.</div></div><div><h3>Review significance</h3><div>Via using <em>in silico</em> databases, bioinformatics analysis, and a thorough literature search to first highlight circRNA as a crucial ncRNA and its biogenesis, and then we explored the connection between circRNA and breast illnesses. In the framework of the review, circRNA sponged-miRNAs axis or as silencers to oncogenic mRNAs were extensively discussed. In the pathophysiology of BC, the circular RNA/microRNA/messenger RNA axis is crucial for the propagation of the disease and resistance that may be targeted for more effective treatment options, in order to confront tumor suppressor and oncogenic mRNAs that are presently regulated by circRNAs in BC. For better patient results, we advised further mechanistic research to elucidate additional ncRNA axis that may be targeted for the therapy of BC and for prognosis/ or early diagnosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}