Molecular Cancer最新文献

{"title":"Deciphering the role of LGALS2: insights into tertiary lymphoid structure-associated dendritic cell activation and immunotherapeutic potential in breast cancer patients","authors":"Shuyu Li, Nan Zhang, Hao Zhang, Zhifang Yang, Quan Cheng, Kang Wei, Meng Zhou, Chenshen Huang","doi":"10.1186/s12943-024-02126-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02126-4","url":null,"abstract":"Recent advances in cancer research have highlighted the pivotal role of tertiary lymphoid structures (TLSs) in modulating immune responses, particularly in breast cancer (BRCA). Here, we performed an integrated analysis of bulk transcriptome data from over 6000 BRCA samples using biological network-based computational strategies and machine learning (ML) methods, and identified LGALS2 as a key marker within TLSs. Single-cell sequencing and spatial transcriptomics uncover the role of LGALS2 in TLS-associated dendritic cells (DCs) stimulation and reveal the complexity of the tumor microenvironment (TME) at both the macro and micro levels. Elevated LGALS2 expression correlates with prolonged survival, which is associated with a robust immune response marked by diverse immune cell infiltration and active anti-tumor pathways leading to a ‘hot’ tumor microenvironment. The colocalization of LGALS2 with TLS-associated DCs and its role in immune activation in BRCA were confirmed by hematoxylin-eosin (HE), immunohistochemistry (IHC), and in vivo validation analyses. The identification of LGALS2 as a key factor in BRCA not only highlights its therapeutic potential in novel TLS-directed immunotherapy but also opens new avenues in patient stratification and treatment selection, ultimately improving clinical management.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"37 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircRNA and lncRNA-encoded peptide in diseases, an update review","authors":"Qian Yi, Jianguo Feng, Weiwu Lan, Houyin shi, Wei Sun, Weichao Sun","doi":"10.1186/s12943-024-02131-7","DOIUrl":"https://doi.org/10.1186/s12943-024-02131-7","url":null,"abstract":"Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"32 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulindac (K-80003) with nab-paclitaxel and gemcitabine overcomes drug-resistant pancreatic cancer","authors":"Cheng-Ke Xie, Cheng-Yu Liao, Hong-Yi Lin, Yong-Ding Wu, Feng-Chun Lu, Xiao-Xiao Huang, Zu-Wei Wang, Ge Li, Cai-Feng Lin, Jian-Fei Hu, Yin-Hao Chen, Qiao-Wei Li, Li-Qun Chen, Hui-Xing Chen, Shi Chen","doi":"10.1186/s12943-024-02128-2","DOIUrl":"https://doi.org/10.1186/s12943-024-02128-2","url":null,"abstract":"The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance’s core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"42 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients","authors":"Sylvia Zöphel, Nadja Küchler, Johanna Jansky, Cora Hoxha, Gertrud Schäfer, Julius J. Weise, Joanne Vialle, Lea Kaschek, Gebhard Stopper, Hermann Eichler, Daniela Yildiz, Alina Moter, Philipp Wendel, Evelyn Ullrich, Claudia Schormann, Torben Rixecker, Onur Cetin, Frank Neumann, Patrick Orth, Moritz Bewarder, Markus Hoth, Lorenz Thurner, Eva C. Schwarz","doi":"10.1186/s12943-024-02123-7","DOIUrl":"https://doi.org/10.1186/s12943-024-02123-7","url":null,"abstract":"Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypically and functionally analyzed blood samples from 46 patients focusing on CD16+ NK cells, CD16+ T cells and CD16+ monocytes. Kaplan-Meier survival curves show a superior progression-free survival (PFS) for patients having more than 1.6% CD16+ T cells (p = 0.02; HR = 0.13 (0.007–0.67)) but an inferior PFS having more than 10.0% CD16+ monocytes (p = 0.0003; HR = 16.0 (3.1-291.9)) at diagnosis. Surprisingly, no correlation with NK cells was found. The increased risk of relapse in the presence of > 10.0% CD16+ monocytes is reversed by the simultaneous occurrence of > 1.6% CD16+ T cells. The unexpectedly strong protective function of CD16+ T cells could be explained by their high antibody-dependent cellular cytotoxicity as quantified by real-time killing assays and single-cell imaging. The combined analysis of CD16+ monocytes (> 10%) and CD16+ T cells (< 1.6%) provided a strong model with a Harrell’s C index of 0.80 and a very strong power of 0.996 even with our sample size of 46 patients. CD16 assessment in the initial blood analysis is thus a precise marker for early relapse prediction. High CD16+ T cell counts have a positive correlation with PFS in aggressive NHL/DLBCL patients (p = 0.02; HR = 0.13, 0.01–0.7). High CD16+ monocyte counts have a negative correlation with PFS in aggressive NHL/DLBCL patients (p = 0.0003; HR = 16.0, 3-292). The combined assessment of CD16+ T cells and CD16+ monocytes accurately predicts PFS in aggressive NHL/DLBCL patients. The strong protective function of CD16+ T cells could be explained by their high antibody-dependent cellular cytotoxicity.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"30 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA-encoded oncogenic PIAS1 variant blocks immunogenic ferroptosis by modulating the balance between SUMOylation and phosphorylation of STAT1","authors":"Xin Zang, Xiao-Yu He, Cheng-Mei Xiao, Qing Lin, Meng-Yue Wang, Cheng-Yan Liu, Ling-Yi Kong, Zhong Chen, Yuan-Zheng Xia","doi":"10.1186/s12943-024-02124-6","DOIUrl":"https://doi.org/10.1186/s12943-024-02124-6","url":null,"abstract":"The clinical response rate to immune checkpoint blockade (ICB) therapy in melanoma remains low, despite its widespread use. Circular non-coding RNAs (circRNAs) are known to play a crucial role in cancer progression and may be a key factor limiting the effectiveness of ICB treatment. The circRNAs that were downregulated after coadministration compared with single administration of PD-1 inhibitor administration were identified through RNA-seq and Ribo-seq, and thus the circPIAS1 (mmu_circ_0015773 in mouse, has_circ_0008378 in human) with high protein coding potential was revealed. Fluorescence in situ hybridization (FISH) assays were conducted to determine the localization of circPIAS1 in human and mouse melanoma cells, as well as its presence in tumor and adjacent tissues of patients. Validation through dual-luciferase reporter assay and LC–MS/MS confirmed the ability of circPIAS1 to encode a novel 108 amino acid polypeptide (circPIAS1-108aa). Specific antisense oligonucleotides (ASOs) targeting the junction site of circPIAS1 were developed to reduce its intracellular levels. Proliferation changes in melanoma cells were assessed using CCK8, EdU, and colony formation assays. The impact of circPIAS1-108aa on the ferroptosis process of melanoma cells was studied through GSH, MDA, and C11-BODIPY staining assays. Western Blot, Immunoprecipitation (IP), and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques were employed to investigate the impact of circPIAS1-108aa on the P-STAT1/SLC7A11/GPX4 signaling pathway, as well as its influence on the balance between STAT1 SUMOylation and phosphorylation. Additionally, a melanoma subcutaneous transplanted tumor mouse model was utilized to examine the combined effect of reducing circPIAS1 levels alongside PD-1 inhibitor. Compared with the group treated with PD-1 inhibitor alone, circPIAS1 was significantly down-regulated in the coadministration group and demonstrated higher protein coding potential. CircPIAS1, primarily localized in the nucleus, was notably upregulated in tumor tissues compared to adjacent tissues, where it plays a crucial role in promoting cancer cell proliferation. This circRNA can encode a unique polypeptide consisting of 108 amino acids, through which it exerts its cancer-promoting function and impedes the effectiveness of ICB therapy. Mechanistically, circPIAS1-108aa hinders STAT1 phosphorylation by recruiting SUMO E3 ligase Ranbp2 to enhance STAT1 SUMOylation, thereby reactivating the transduction of the SLC7A11/GPX4 signaling pathway and restricting the immunogenic ferroptosis induced by IFNγ. Furthermore, the combination of ASO-circPIAS1 with PD-1 inhibitor effectively inhibits melanoma growth and significantly enhances the efficacy of immune drugs in vivo. Our study uncovers a novel mechanism regarding immune evasion in melanoma driven by a unique 108aa peptide encoded by circPIAS1 in melanoma that dramatically hinders immunogenic ferroptosis triggered by ICB therapy via modulating","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"1 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy","authors":"Jun-xiao Shi, Zhi-chao Zhang, Hao-zan Yin, Xian-jie Piao, Cheng-hu Liu, Qian-jia Liu, Jia-cheng Zhang, Wen-xuan Zhou, Fu-chen Liu, Fu Yang, Yue-fan Wang, Hui Liu","doi":"10.1186/s12943-024-02132-6","DOIUrl":"https://doi.org/10.1186/s12943-024-02132-6","url":null,"abstract":"The pursuit of innovative therapeutic strategies in oncology remains imperative, given the persistent global impact of cancer as a leading cause of mortality. Immunotherapy is regarded as one of the most promising techniques for systemic cancer therapies among the several therapeutic options available. Nevertheless, limited immune response rates and immune resistance urge us on an augmentation for therapeutic efficacy rather than sticking to conventional approaches. Ferroptosis, a novel reprogrammed cell death, is tightly correlated with the tumor immune environment and interferes with cancer progression. Highly mutant or metastasis-prone tumor cells are more susceptible to iron-dependent nonapoptotic cell death. Consequently, ferroptosis-induction therapies hold the promise of overcoming resistance to conventional treatments. The most prevalent post-transcriptional modification, RNA m6A modification, regulates the metabolic processes of targeted RNAs and is involved in numerous physiological and pathological processes. Aberrant m6A modification influences cell susceptibility to ferroptosis, as well as the expression of immune checkpoints. Clarifying the regulation of m6A modification on ferroptosis and its significance in tumor cell response will provide a distinct method for finding potential targets to enhance the effectiveness of immunotherapy. In this review, we comprehensively summarized regulatory characteristics of RNA m6A modification on ferroptosis and discussed the role of RNA m6A-mediated ferroptosis on immunotherapy, aiming to enhance the effectiveness of ferroptosis-sensitive immunotherapy as a treatment for immune-resistant malignancies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"22 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PBA2, a novel inhibitor of the β-catenin/CBP pathway, eradicates chronic myeloid leukemia including BCR-ABL T315I mutation","authors":"Ke Yang, Kai Fu, Hong Zhang, Xiaokun Wang, Kenneth K.W. To, Caibo Yang, Fang Wang, Zhe-Sheng Chen, Liwu Fu","doi":"10.1186/s12943-024-02129-1","DOIUrl":"https://doi.org/10.1186/s12943-024-02129-1","url":null,"abstract":"BCR-ABL is a constitutively active tyrosine kinase that stimulates multiple downstream signaling pathways to promote the survival and proliferation of chronic myeloid leukemia (CML) cells. The clinical application of specific BCR-ABL tyrosine kinase inhibitors (TKIs) has led to significantly improved prognosis and overall survival in CML patients compared to previous treatment regimens. However, direct targeting of BCR-ABL does not eradicate CML cells expressing T315I-mutated BCR-ABL. Our previous study revealed that inhibiting CREB binding protein (CBP) is efficacious in activating β-catenin/p300 signaling, promoting cell differentiation and inducing p53/p21-dependent senescence regardless of BCR-ABL mutation status. We hypothesize that the specific inhibition of CBP may represent a novel strategy to promote β-catenin/p300-mediated differentiation and suppress cancer cell proliferation for treating CML patients. The anticancer efficacy of PBA2, a novel CBP inhibitor, in CML cells expressing wild-type or T315I-mutated BCR-ABL was investigated in vitro and in vivo. Cell differentiation was determined by the nitroblue tetrazolium (NBT) reduction assay. The extent of cellular senescence was assessed by senescence-associated β-galactosidase (SA-β-Gal) activity. Cytotoxicity was measured by MTS assay. RNA interference was performed to evaluate the cell proliferation effects of CBP knockdown. The interaction of β-catenin and CBP/p300 was examined by co-immunoprecipitation assay. PBA2 exhibited significantly higher anticancer effects than imatinib in CML cells harboring either wild-type or T315I-mutated BCR-ABL both in vitro and in vivo. Mechanistically, PBA2 reduced CBP expression and promoted β-catenin-p300 interaction to induce cell differentiation and senescence. Our data supported the rational treatment of CML by inhibiting the β-catenin/CBP pathway regardless of BCR-ABL mutation status.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"30 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Technical University of Munich Cancer Center - elevating cancer treatment through science","authors":"Judith S. Hecker, Hana Algül, Anna L. Illert, Florian Bassermann","doi":"10.1186/s12943-024-02127-3","DOIUrl":"https://doi.org/10.1186/s12943-024-02127-3","url":null,"abstract":"&lt;p&gt;The Technical University of Munich and the Ludwig Maximilian University Munich are both top-ranked universities on the national and international level and distinguished as “elite universities” within the national German Research Foundation (DFG)-funded excellence program. Both sites are established and leading cancer research institutions in Europe that have joined forces within the Comprehensive Cancer Center Munich (CCCM). This positions CCCM as a prominent global leader dedicated to advancing excellence in research and education in the field of cancer. The clear vision and goal of the CCCM is the guidance of clinical trials from inception to completion, focusing on the best research and science to strengthen the development of biologically and technologically innovative therapies and diagnostics. Supplemented by multidisciplinary programs for bi-directional translation, proof-of-concept studies and clinical research programs, these focus areas are further strengthened by a dedicated infrastructure for data management and artificial intelligence (AI). Patient participation is another key focus of the CCCM’s joint activities, enhanced through novel establishments such as a Patient Advisory Board (PAB) which advocates for patients and families, identifies new areas for action, and addresses challenges relevant to them. Collaborative committees and task forces provide recommendations to the CCCM to support these efforts. Further, the CCCM strongly emphasizes its clinical and scientific interactions with oncologists outside the university hospitals. Continuous exchange of information on prevention, cancer-related physical/psychological challenges, and recent developments in cancer medicine and treatment modalities as well as outreach activities are pursued at multiple levels.&lt;/p&gt;&lt;p&gt;At the Technical University of Munich (TUM), the Comprehensive Cancer Center (CCCM-TUM) is deeply committed to fostering collaboration across all disciplines and departments focused on cancer medicine. As a vital partner of the TUM Cancer Center, CCCM-TUM plays a key role in the overarching governance within the faculty, offering stakeholders opportunities to collaborate and translate discoveries into innovations. In this capacity, it coordinates all activities related to cancer medicine and advocates for the interests of numerous basic and clinical researchers.&lt;/p&gt;&lt;p&gt;In this article, we would like to highlight some TUM specific activities, particularly focusing on the preclinical and clinical structures of the Department of Hematology/Oncology (https://med3.mri.tum.de). The content thus does not claim to provide a complete representation of research activities at the TUM Cancer Center.&lt;/p&gt;&lt;p&gt;Structurally, the TranslaTUM (Central Institute for Translational Cancer Research: https://www.translatum.tum.de) stands out as a uniquely established central research institute situated in close proximity to the TUM University Hospital. This initiative is dedicated to fostering","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircLIFRSA/miR-1305/PTEN axis attenuates malignant cellular processes in non-small cell lung cancer by regulating AKT phosphorylation","authors":"Meina Jiang, Huihui Bai, Shuai Fang, Chengwei Zhou, Weiyu Shen, Zhaohui Gong","doi":"10.1186/s12943-024-02120-w","DOIUrl":"https://doi.org/10.1186/s12943-024-02120-w","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is typically diagnosed at advanced stages, which limits the effectiveness of therapeutic interventions. The present study aimed to explore the role of the newly identified circLIFRSA in the PTEN/AKT signaling pathway and its involvement in the malignant processes of NSCLC. CircLIFRSA expression was identified through microarray analysis, and its levels in NSCLC samples were quantified by RT-qPCR. The impact of circLIFRSA on cell growth, proliferation, apoptosis, and cell cycle were evaluated by MTT assay, colony formation assay, and flow cytometry. Additionally, Western blotting was employed to analyze the expression of PTEN and phosphorylated AKT (pAKT) in NSCLC cells. The expression of circLIFRSA was found to be significantly reduced in NSCLC cells and tissues. This downregulation correlated with various clinicopathological characteristics and indicated its potential as an early diagnostic biomarker for NSCLC. Importantly, circLIFRSA was shown to inhibit cell growth and proliferation while promoting apoptosis in NSCLC cells. Mechanically, circLIFRSA was found to attenuate the malignant processes of NSCLC cells via the miR-1305/PTEN axis and the suppression of AKT phosphorylation. These findings indicate that circLIFRSA/miR-1305/PTEN axis attenuates malignant processes by regulating AKT phosphorylation, and provide new insights into the potential of circLIFRSA as a biomarker for early diagnosis and as a promising therapeutic target in NSCLC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"11 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charting the metabolic biogeography of the colorectum in cancer: challenging the right sided versus left sided classification","authors":"Abhishek Jain, Montana T. Morris, Domenica Berardi, Trisha Arora, Xavier Domingo-Almenara, Philip B. Paty, Nicholas J. W. Rattray, Daniel Kerekes, Lingeng Lu, Sajid A. Khan, Caroline H. Johnson","doi":"10.1186/s12943-024-02133-5","DOIUrl":"https://doi.org/10.1186/s12943-024-02133-5","url":null,"abstract":"Colorectal cancer (CRC) is conventionally classified as right sided, left sided, and rectal cancer. Clinicopathological, molecular features and risk factors do not change abruptly along the colorectum, and variations exist even within the refined subsites, which may contribute to inconsistencies in the identification of clinically relevant CRC biomarkers. We generated a CRC metabolome map to describe the association between metabolites, diagnostic and survival heterogeneity in cancers of different subsites of the colorectum. Utilizing 372 patient-matched tumor and normal mucosa tissues, liquid chromatography-mass spectrometry was applied to examine metabolomic profiles along seven subsites of the colorectum: cecum (n = 63), ascending colon (n = 44), transverse colon (n = 32), descending colon (n = 28), sigmoid colon (n = 75), rectosigmoid colon (n = 38), and rectum (n = 92). 39 and 70 significantly altered metabolites (including bile acids, lysophosphatidylcholines and lysophosphatidylethanolamines) among tumors and normal mucosa, respectively, showed inter-subsite metabolic heterogeneity between CRC subsites. Gradual changes in metabolite abundances with significantly linear trends from cecum to rectum were observed: 23 tumor-specific metabolites, 30 normal mucosa-specific metabolites, and 15 metabolites in both tumor and normal mucosa, had concentration gradients across the colorectum, and is disease status dependent. The metabolites that showed a linear trend included bile acids, amino acids, lysophosphatidylcholines, and lysophosphatidylethanolamines. Comparison of tumors to patient-matched normal mucosa revealed metabolite changes exclusive to each subsite, thereby further highlighting differences in cancer metabolism across the 7 subsites of the colorectum. Furthermore, metabolites associated with survival were different and unique to each subsite. Finally, an interactive and publicly accessible CRC metabolome database was designed to enable access and utilization of this rich data resource ( https://colorectal-cancer-metabolome.com/yale-university ). Gradual changes exist in metabolite abundances from the cecum to the rectum. The association between patient survival and distinct metabolites with anatomic subsite of the colorectum, reveals differences between cancers across the colorectum. These inter-subsite metabolic heterogeneities enrich the current understanding and substantiate previous studies that have challenged the conventional classification of right-sided, left-sided, and rectal cancers, by identifying specific metabolites that offer new biological insights into CRC subsite heterogeneity. The database designed in this study will enable researchers to delve into granular information on the CRC metabolome, which until now has not been available.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"17 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}