Cancer letters最新文献

{"title":"Circadian disruption in cancer hallmarks: Novel insight into the molecular mechanisms of tumorigenesis and cancer treatment","authors":"Zhaokai Zhou ,&nbsp;Ruiqi Zhang ,&nbsp;Yuyuan Zhang ,&nbsp;Yudi Xu ,&nbsp;Ruizhi Wang ,&nbsp;Shuang Chen ,&nbsp;Yingying Lv ,&nbsp;Yifeng Chen ,&nbsp;Yuqing Ren ,&nbsp;Peng Luo ,&nbsp;Quan Cheng ,&nbsp;Hui Xu ,&nbsp;Siyuan Weng ,&nbsp;Anning Zuo ,&nbsp;Yuhao Ba ,&nbsp;Shutong Liu ,&nbsp;Xinwei Han ,&nbsp;Zaoqu Liu","doi":"10.1016/j.canlet.2024.217273","DOIUrl":"10.1016/j.canlet.2024.217273","url":null,"abstract":"<div><div>Circadian rhythms are 24-h rhythms governing temporal organization of behavior and physiology generated by molecular clocks composed of autoregulatory transcription-translation feedback loops (TTFLs). Disruption of circadian rhythms leads to a spectrum of pathologies, including cancer by triggering or being involved in different hallmarks. Clock control of phenotypic plasticity involved in tumorigenesis operates in aberrant dedifferentiating to progenitor-like cell states, generation of cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) events. Circadian rhythms might act as candidates for regulatory mechanisms of cellular senescent and functional determinants of senescence-associated secretory phenotype (SASP). Reciprocal control between clock and epigenetics sheds light on post-transcriptional regulation of circadian rhythms and opens avenues for novel anti-cancer strategies. Additionally, disrupting circadian rhythms influences microbiota communities that could be associated with altered homeostasis contributing to cancer development. Herein, we summarize recent advances in support of the nexus between disruptions of circadian rhythms and cancer hallmarks of new dimensions, thus providing novel perspectives on potentially effective treatment approaches for cancer management.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217273"},"PeriodicalIF":9.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280532","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":"FABP4-mediated lipid metabolism promotes TNBC progression and breast cancer stem cell activity","authors":"Liya Yu ,&nbsp;Wei Wei ,&nbsp;Jian Lv ,&nbsp;Yu Lu ,&nbsp;Zhihua Wang ,&nbsp;Cheguo Cai","doi":"10.1016/j.canlet.2024.217271","DOIUrl":"10.1016/j.canlet.2024.217271","url":null,"abstract":"<div><div>Metabolic remodeling is a pivotal feature of cancer, with cancer stem cells frequently showcasing distinctive metabolic behaviors. Nonetheless, understanding the metabolic intricacies of triple-negative breast cancer (TNBC) and breast cancer stem cells (BCSCs) has remained elusive. In this study, we meticulously characterized the metabolic profiles of TNBC and BCSCs and delved into their potential implications for TNBC treatment. Our findings illuminated the robust lipid metabolism activity within TNBC tumors, especially in BCSCs. Furthermore, we discovered that Fabp4, through its mediation of fatty acid uptake, plays a crucial role in regulating TNBC lipid metabolism. Knocking down <em>Fabp4</em> or inhibiting its activity significantly suppressed TNBC tumor progression in both the <em>MMTV-Wnt1</em> spontaneous TNBC model and the TNBC patient-derived xenograft model. Mechanistically, Fabp4's influence on TNBC tumor progression was linked to its regulation of mitochondrial stability, the CPT1-mediated fatty acid oxidation process, and ROS production. Notably, in a high-fat diet model, Fabp4 deficiency proved to be a substantial inhibitor of obesity-accelerated TNBC progression. Collectively, these findings shed light on the unique metabolic patterns of TNBC and BCSCs, underscore the biological significance of Fabp4-mediated fatty acid metabolism in governing TNBC progression, and offer a solid theoretical foundation for considering metabolic interventions in breast cancer treatment.</div></div><div><h3>Significance</h3><div>Triple-negative breast cancer progression and breast cancer stem cell activity can be restricted by targeting a critical regulator of lipid responses, FABP4.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217271"},"PeriodicalIF":9.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280534","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":"Targeting RNA helicase DDX3X with a small molecule inhibitor for breast cancer bone metastasis treatment","authors":"Paul T. Winnard Jr. ,&nbsp;Farhad Vesuna ,&nbsp;Guus M. Bol ,&nbsp;Kathleen L. Gabrielson ,&nbsp;Georgia Chenevix-Trench ,&nbsp;Natalie D. ter Hoeve ,&nbsp;Paul J. van Diest ,&nbsp;Venu Raman","doi":"10.1016/j.canlet.2024.217260","DOIUrl":"10.1016/j.canlet.2024.217260","url":null,"abstract":"<div><div>Patients who present with breast cancer bone metastasis only have limited palliative treatment strategies and efficacious drug treatments are needed. In breast cancer patient data, high levels of the RNA helicase DDX3 are associated with poor overall survival and bone metastasis. Consequently, our objective was to target DDX3 in a mouse breast cancer bone metastasis model using a small molecule inhibitor of DDX3, RK-33. Histologically confirmed live imaging indicated no bone metastases in the RK-33 treated cohort, as opposed to placebo-treated mice. We generated a cell line from a bone metastatic lesion in mouse and found that it along with a patient-derived bone metastasis cell line gained resistance to conventional chemotherapeutics but not to RK-33. Finally, differential levels of DDX3 were observed in breast cancer patient metastatic bone samples. Overall, this study indicates that DDX3 is a relevant clinical target in breast cancer bone metastasis and that RK-33 can be a safe and effective treatment for these patients.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217260"},"PeriodicalIF":9.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280546","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":"Complement is increased in treatment resistant rectal cancer and modulates radioresistance","authors":"Rebecca M. O'Brien ,&nbsp;Sebastian Meltzer ,&nbsp;Croí E. Buckley ,&nbsp;Aisling B. Heeran ,&nbsp;Timothy S. Nugent ,&nbsp;Noel E. Donlon ,&nbsp;John V. Reynolds ,&nbsp;Anne Hansen Ree ,&nbsp;Kathrine Røe Redalen ,&nbsp;Adnan Hafeez ,&nbsp;Diarmuid S. O’Ríordáin ,&nbsp;Robert A. Hannon ,&nbsp;Paul Neary ,&nbsp;Reza Kalbassi ,&nbsp;Brian J. Mehigan ,&nbsp;Paul H. McCormick ,&nbsp;Cara Dunne ,&nbsp;Michael E. Kelly ,&nbsp;John O. Larkin ,&nbsp;Jacintha O'Sullivan ,&nbsp;Niamh Lynam-Lennon","doi":"10.1016/j.canlet.2024.217253","DOIUrl":"10.1016/j.canlet.2024.217253","url":null,"abstract":"<div><p>Resistance to neoadjuvant chemoradiation therapy (neo-CRT) is a significant clinical problem in the treatment of locally advanced rectal cancer. Identification of novel therapeutic targets and biomarkers predicting therapeutic response is required to improve patient outcomes. Increasing evidence supports a role for the complement system in resistance to anti-cancer therapy. In this study, increased expression of complement effectors C3 and C5 and increased production of anaphylatoxins, C3a and C5a, was observed in radioresistant rectal cancer cells. Modulation of the central complement effector, C3, was demonstrated to functionally alter the radioresponse, with C3 overexpression significantly enhancing radioresistance, whilst C3 inhibition significantly increased sensitivity to a clinically-relevant dose of radiation. Inhibition of C3 was demonstrated to increase DNA damage and alter cell cycle distribution, mediating a shift towards a radiosensitive cell cycle phenotype suggesting a role for C3 in reprogramming of the tumoural radioresponse. Expression of the complement effectors C3 and C5 was significantly increased in human rectal tumour tissue, as was expression of CFB, a component of the alternative pathway of activation. Elevated levels of C3a and C5b-9 in pre-treatment sera from rectal cancer patients was associated with subsequent poor responses to neo-CRT and poorer survival. Together these data demonstrate a role for complement in the radioresistance of rectal cancer and identify key complement components as potential biomarkers predicting response to neo-CRT and outcome in rectal cancer.</p></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217253"},"PeriodicalIF":9.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271839","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":"Single-nucleus sequencing unveils heterogeneity in renal cell carcinomas microenvironment: Insights into pathogenic origins and treatment-responsive cellular subgroups","authors":"Cong Zhang ,&nbsp;Xin Gou ,&nbsp;Guichuan Lai ,&nbsp;Kangjie Li ,&nbsp;Xin Zhu ,&nbsp;Nian Liu ,&nbsp;Youlin Kuang ,&nbsp;Ke Ren ,&nbsp;Yongpeng Xie ,&nbsp;Yungang Xu ,&nbsp;Xiaoni Zhong ,&nbsp;Biao Xie","doi":"10.1016/j.canlet.2024.217259","DOIUrl":"10.1016/j.canlet.2024.217259","url":null,"abstract":"<div><h3>Background</h3><p>Different individuals with renal cell carcinoma (RCC) exhibit substantial heterogeneity in histomorphology, genetic alterations in the proteome, immune cell infiltration patterns, and clinical behavior.</p></div><div><h3>Objectives</h3><p>This study aims to use single-nucleus sequencing on ten samples (four normal, three clear cell renal cell carcinoma (ccRCC), and three chromophobe renal cell carcinoma (chRCC)) to uncover pathogenic origins and prognostic characteristics in patients with RCC.</p></div><div><h3>Methods</h3><p>By using two algorithms, inferCNV and k-means, the study explores malignant cells and compares them with the normal group to reveal their origins. Furthermore, we explore the pathogenic factors at the gene level through Summary-data-based Mendelian Randomization and co-localization methods. Based on the relevant malignant markers, a total of 212 machine-learning combinations were compared to develop a prognostic signature with high precision and stability. Finally, the study correlates with clinical data to investigate which cell subtypes may impact patients’ prognosis.</p></div><div><h3>Results &amp; conclusion</h3><p>Two main origin tumor cells were identified: Proximal tubule cell B and Intercalated cell type A, which were highly differentiated in epithelial cells, and three gene loci were determined as potential pathogenic genes. The best malignant signature among the 212 prognostic models demonstrated high predictive power in ccRCC: (AUC: 0.920 (1-year), 0.920 (3-year) and 0.930 (5-year) in the training dataset; 0.756 (1-year), 0.828 (3-year), and 0.832 (5-year) in the testing dataset. In addition, we confirmed that LYVE1⁺ tissue-resident macrophage and TOX⁺ CD8 significantly impact the prognosis of ccRCC patients, while monocytes play a crucial role in the prognosis of chRCC patients.</p></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217259"},"PeriodicalIF":9.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239788","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":"A rigorous multi-laboratory study of known PDAC biomarkers identifies increased sensitivity and specificity over CA19-9 alone","authors":"Brian Haab ,&nbsp;Lu Qian ,&nbsp;Ben Staal ,&nbsp;Maneesh Jain ,&nbsp;Johannes Fahrmann ,&nbsp;Christine Worthington ,&nbsp;Denise Prosser ,&nbsp;Liudmila Velokokhatnaya ,&nbsp;Camden Lopez ,&nbsp;Runlong Tang ,&nbsp;Mark W. Hurd ,&nbsp;Gopalakrishnan Natarajan ,&nbsp;Sushil Kumar ,&nbsp;Lynette Smith ,&nbsp;Sam Hanash ,&nbsp;Surinder K. Batra ,&nbsp;Anirban Maitra ,&nbsp;Anna Lokshin ,&nbsp;Ying Huang ,&nbsp;Randall E. Brand","doi":"10.1016/j.canlet.2024.217245","DOIUrl":"10.1016/j.canlet.2024.217245","url":null,"abstract":"<div><p>A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p &lt; 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p &lt; 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial.</p></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217245"},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304383524006402/pdfft?md5=e23974a905a5d55dab2d38bc7ec246e0&pid=1-s2.0-S0304383524006402-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting tumor mechanomedicine for lung cancer treatment","authors":"Antonios N. Gargalionis,&nbsp;Kostas A. Papavassiliou,&nbsp;Efthimia K. Basdra,&nbsp;Athanasios G. Papavassiliou","doi":"10.1016/j.canlet.2024.217229","DOIUrl":"10.1016/j.canlet.2024.217229","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217229"},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232332","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":"MATR3 promotes liver cancer progression by suppressing DHX58–mediated type I interferon response","authors":"Zhaofeng Xiao ,&nbsp;Huan Chen ,&nbsp;Nan Xu ,&nbsp;Yiyuan Chen ,&nbsp;Shuai Wang ,&nbsp;Xiao Xu","doi":"10.1016/j.canlet.2024.217231","DOIUrl":"10.1016/j.canlet.2024.217231","url":null,"abstract":"<div><p>MATR3 is a nuclear matrix protein implicated in various cancers; however, its specific role in tumor progression remains unclear. The study utilized the TCGA database to reveal that MATR3 expression is upregulated in liver cancer and is correlated with poor prognosis. Functionally, MATR3 promoted liver cancer cell proliferation and metastasis. Comprehensive RNA sequencing analysis showed that MATR3 significantly affected the type I IFN signaling pathway and DHX58 is a downstream target of MATR3. Further experiments showed that MATR3 bound to DHX58 mRNA through its RRM structural domain and recruited YTHDF2, an m⁶A reader, leading to degradation of DHX58 mRNA and suppression of the type I IFN signaling pathway. The knockout of MATR3 in liver cancer cells triggered a natural immune response that stimulated CD8⁺ T cells to eliminate liver cancer cells. This study demonstrated that MATR3 downregulates type I IFN signaling in liver cancer cells through m⁶A modification and inhibits immune cell infiltration within tumors. These findings expand our understanding of the role of MATR3 in liver cancer.</p></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217231"},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304383524006268/pdfft?md5=bf6f0fa94e0c581094108534fb5a7b3f&pid=1-s2.0-S0304383524006268-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macroautophagy/autophagy promotes resistance to KRASG12D-targeted therapy through glutathione synthesis","authors":"Leng Han ,&nbsp;Lingjun Meng ,&nbsp;Jiao Liu ,&nbsp;Yangchun Xie ,&nbsp;Rui Kang ,&nbsp;Daniel J. Klionsky ,&nbsp;Daolin Tang ,&nbsp;Yuanyuan Jia ,&nbsp;Enyong Dai","doi":"10.1016/j.canlet.2024.217258","DOIUrl":"10.1016/j.canlet.2024.217258","url":null,"abstract":"<div><p><em>KRAS</em>^{<em>G12D</em>} mutation-driven pancreatic ductal adenocarcinoma (PDAC) represents a major challenge in medicine due to late diagnosis and treatment resistance. Here, we report that macroautophagy (hereafter autophagy), a cellular degradation and recycling process, contributes to acquired resistance against novel KRAS^G12D-targeted therapy. The KRAS^G12D protein inhibitor MRTX1133 induces autophagy in <em>KRAS</em>^{<em>G12D</em>}-mutated PDAC cells by blocking MTOR activity, and increased autophagic flux prevents apoptosis. Mechanistically, autophagy facilitates the generation of glutamic acid, cysteine, and glycine for glutathione synthesis. Increased glutathione levels reduce reactive oxygen species production, which impedes CYCS translocation from mitochondria to the cytosol, ultimately preventing the formation of the APAF1 apoptosome. Consequently, genetic interventions (utilizing <em>ATG5</em> or <em>BECN1</em> knockout) or pharmacological inhibition of autophagy (with chloroquine, bafilomycin A₁, or spautin-1) enhance the anticancer activity of MRTX1133 <em>in vitro</em> and in various animal models (subcutaneous, patient-derived xenograft, and orthotopic). Moreover, the release of histones by apoptotic cells triggers an adaptive immune response when combining an autophagy inhibitor with MRTX1133 in immunocompetent mice. These findings establish a new strategy to overcome KRAS^G12D-targeted therapy resistance by inhibiting autophagy-dependent glutathione synthesis.</p></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217258"},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304383524006530/pdfft?md5=04097899eb61102cd2f3f2ea0ed89db5&pid=1-s2.0-S0304383524006530-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFβ2 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance","authors":"Shule Xie ,&nbsp;Yingru Li ,&nbsp;Lianxi Mai ,&nbsp;Xiaolin Gao ,&nbsp;Guoxin Huang ,&nbsp;Wenhao Sun ,&nbsp;Liang Qiao ,&nbsp;Bowen Li ,&nbsp;Youyuan Wang ,&nbsp;Zhaoyu Lin","doi":"10.1016/j.canlet.2024.217230","DOIUrl":"10.1016/j.canlet.2024.217230","url":null,"abstract":"<div><div>Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFβ2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFβ2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFβ2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"604 ","pages":"Article 217230"},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280531","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}