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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

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

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

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