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Poly(A)-specific RNase(PARN)generates and regulates miR-125a-5p 3’-isoforms,displaying an altered expression in breast cancer

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1805-1807页

作者： Luisa Tomasello Shoshanah m.Holub Giovanni Nigita Rosario Distefano carlo m.croce Department of Cancer Biology and Genetics The Ohio State UniversityColumbusOHUSA Department of Internal medicine Division of HematologyThe Ohio State UniversityColumbusOHUSA

Dear Editor,microRNAs(miRNAs)are small non-coding RNAs crucial for post-transcriptional gene regulation,processed from primary miRNA transcripts by Drosha and Dicer.1 Latest advancements in Next Generation Sequencing highlighted the existence of miRNA isoforms(isomiRs)resulting from alternative processing,RNA editing,or post-transcriptional modifications.

关键词： breast cancer advancement

PDCD1(PD-1)is a direct target of miR-15a-5p and miR-16-5p

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Signal Transduction and Targeted Therapy 2022年第2期7卷 366-368页

作者： Alexey Palamarchuk Liudmyla Tsyba Luisa Tomasello Yuri Pekarsky carlo m.croce Department of Cancer Biology and Genetics Comprehensive Cancer CenterThe Ohio State University ColumbusOH 43210USA

Dear Editor,Programmed cell death protein 1(PD-1;encoded by the PDCD1 gene),mostly expressed on activated T cells,is an important receptor in T-cell immunity.1–3 Together with programmed deathligand 1(PD-L1:encoded b... 详细信息

关键词： PDCD1 death conditions.

miRNAs in precancerous lesions of the gastrointestinal tract

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World Journal of Gastroenterology 2011年第48期17卷 5231-5239页

作者： matteo Fassan carlo m croce massimo Rugge Department of medical Diagnostic Sciences and Special Therapies Surgical Pathology and Cytopathology Unit University of Padova Department of Oncological and Surgical Sciences General Oncology Unit University of Padova Comprehensive Cancer Center Ohio State University Istituto Oncologico del Veneto-IOV-IRCCS

In spite of the well-established understanding of the phenotypic lesions occurring in the shift from native epithelia to invasive （adeno） carcinoma, the molecular b/ping of the precancerous changes in the gastrointes- tinal tract remains unreliable. In recent years, no biomarkers have aroused as much interest as the miRNAs, a class of non-coding RNA molecules that function as endogenous silencers of numerous target genes. Aberrant miRNA expression is a hallmark of human disease, including cancer. Unlike most mRNAs, miRNAs are both long-living in vivo and very stable in vitro. Such charac- teristics allow their testing in paraffin-embedded tissue samples, which is essential in the biological profiling of small （phenotypically characterized） preneoplastic lesions of the gastrointestinal tract （as well as in other fields of human pathology）. The upcoming challenge lies in the reliable identification of disease-specific targets of dysregulated miRNAs, to enable miRNA testing in the clinical management of the secondary prevention of gastrointestinal cancer.

关键词： miRNA Dysplasia Barrett's esophagus Atro-phic gastritis Inflammatory bowel disease

Role of the miR-301a/Fra-2/GLIPR1 axis in lung cancer cisplatin resistance

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Signal Transduction and Targeted Therapy 2023年第2期8卷 377-380页

作者： Gian Luca Rampioni Vinciguerra marina Capece Rosario Distefano Giovanni Nigita Andrea Vecchione Francesca Lovat carlo m.croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbusOH43210USA Department of Clinical and molecular medicine University of Rome‘Sapienza’Sant’Andrea HospitalRome00189Italy

Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related mortality ***-based chemotherapy represents the main treatment,despite about the 70%of tumors are intrinsically *** the mechanisms of platinum-re... 详细信息

关键词： lung cancer chemotherapy

Therapeutic advances of targeting receptor tyrosine kinases in cancer

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Signal Transduction and Targeted Therapy 2024年第9期9卷 3765-3815页

作者： Ciprian Tomuleasa Adrian-Bogdan Tigu Raluca munteanu Cristian-Silviu moldovan David Kegyes Anca Onaciu Diana Gulei Gabriel Ghiaur Hermann Einsele carlo m.croce medfuture Research Center for Advanced medicine Iuliu Hatieganu University of Medicine and PharmacyCluj-NapocaRomania Department of Hematology Iuliu Hatieganu University of Medicine and PharmacyCluj NapocaRomania Department of Hematology Ion Chiricuta Clinical Cancer CenterCluj NapocaRomania Academy of Romanian Scientists Ilfov 3050044 BucharestRomania Department of Leukemia Sidney Kimmel Cancer Center at Johns HopkinsJohns Hopkins University School of MedicineBaltimoreMDUSA Universitätsklinikum Würzburg Medizinische Klinik IIWürzburgGermany Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbusOHUSA

Receptor tyrosine kinases(RTKs),a category of transmembrane receptors,have gained significant clinical attention in oncology due to their central role in cancer *** alterations,including mutations,amplifications,and overexpression of certain RTKs,are critical in creating environments conducive to tumor *** their discovery,extensive research has revealed how RTK dysregulation contributes to oncogenesis,with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation,survival and *** findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in *** a result,RTKs have emerged as primary targets in anticancer therapeutic *** the past two decades,this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors(TKIs),now effectively utilized in treating various cancer *** this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of *** explored the various alterations and overexpression of specific receptors across different malignancies,with special attention dedicated to the examination of current RTK inhibitors,highlighting their role as potential targeted *** integrating the latest research findings and clinical evidence,we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.

关键词： alterations finding gained

Pleiotropic tumor suppressor functions of WWOX antagonize metastasis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2033-2042页

作者： Saleh Khawaled Giovanni Nigita Rosario Distefano Sara Oster Sung-Suk Suh Yoav Smith Abed Khalaileh Yong Peng carlo m.croce Tamar Geiger Victoria L.Seewaldt Rami I.Aqeilan Lautenberg Center for Immunology and Cancer Research Hebrew University-Hadassah Medical SchoolIMRICJerusalemIsrael Department of Cancer Biology and Genetics Wexner Medical CenterThe Ohio State UniversityColumbusOHUSA Department of Bioscience Mokpo National UniversityMuanRepublic of Korea Genomic Data Analysis Unit Hebrew University-Hadassah Medical SchoolJerusalemIsrael Department of Surgery Hadassah Medical CenterJerusalemIsrael Department of Thoracic Surgery State Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation Center for Biotherapy610041 ChengduChina Department of Human molecular Genetics and Biochemistry Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Population Sciences City of Hope Comprehensive Cancer CenterDuarteCAUSA

Tumor progression and metastasis are the major causes of death among cancer associated *** cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition(EmT).Acquirement of these various hallmarks rely on different cellular pathways,including TGF-βand Wnt ***,we reported that WW domain-containing oxidoreductase(WWOX)acts as a tumor suppressor and has anti-metastatic activities involving regulation of several key microRNAs(miRNAs)in triple-negative breast cancer(TNBC).Here,we report that WWOX restoration in highly metastatic mDA-mB435S cancer cells alters mRNA expression profiles;further,WWOX interacts with various proteins to exert its tumor suppressor *** alignment and analysis of gene and miRNA expression in these cells revealed profound changes in cellular pathways mediating adhesion,invasion and *** further demonstrate that WWOX,through regulation of miR-146a levels,regulates SmAD3,which is a member of the TGF-βsignaling ***,proteomic analysis of WWOX partners revealed regulation of the Wnt-signaling activation through physical interaction with ***,these findings underscore a significant role for WWOX in antagonizing metastasis,further highlighting its role and therapeutic potential in suppressing tumor progression.

关键词： WWOX metastasis suppressor

Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat carlo m.croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and molecular medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

易位的和未易位的C-myC致癌基因在Burkitt氏淋巴瘤中的表达有所不同

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基础医学与临床 1984年第2期 58-59页

作者： carlo m.croce ,谭景莹

大约有90％的Burkitt氏淋巴瘤中恶性细胞在8号和14号染色体间易位[t（8;14）],其余10％的细胞在t（2;8）易位或是t（8;22）易位,8号染色体的断裂点都是在q24带。检测小鼠细胞和Burkitt氏淋巴瘤体细胞的杂交细胞发现t（8;14）易位时,淋... 详细信息

大约有90％的Burkitt氏淋巴瘤中恶性细胞在8号和14号染色体间易位[t（8;14）],其余10％的细胞在t（2;8）易位或是t（8;22）易位,8号染色体的断裂点都是在q24带。检测小鼠细胞和Burkitt氏淋巴瘤体细胞的杂交细胞发现t（8;14）易位时,淋巴瘤细胞在14号染色体的断裂点是在免疫球蛋白重链区内,重链可变区VH基因从正常地定位的14号染色体易位到淋巴瘤细胞内有缺失的8号染色体上。禽类髓细胞瘤病病毒转化基因V-myc

关键词：淋巴瘤致癌基因染色体 Burkitt C-myC 易位

ERK激酶磷酸化exportin-5调控miRNA生物合成的研究

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ERK激酶磷酸化exportin-5调控miRNA生物合成的研究