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Smaranda Buduru,1 Alina-Andreea Zimta,2 Cristina Ciocan,2 Cornelia Braicu,3 Diana Dudea,4 Alexandra Iulia Irimie,4 Ioana Berindan-Neagoe2,3,5 1Department of Prosthetics and Dental Materials, Faculty of Dental Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2MEDFUTURE – Research Center for Advanced Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3Research Center for Functional Genomics and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Department of Prosthetic Dentistry and Dental Materials, Division Dental Propaedeutic, Aesthetic, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 5Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania Abstract: Over the last few decades, the incidence of oral cancer has gradually increased, due to the negative influence of environmental factors and also abnormalities within the genome. The main issues in oral cancer treatment consist in surpassing resistance and recurrence. However, continuous discovery of altered signaling pathways in these tumors provides valuable information for the identification of novel gene candidates targeted in personalized therapy. RNA interference (RNAi) is a natural mechanism that involves small interfering RNA (siRNA); this can be exploited in biomedical research by using natural or synthetic constructs for activation of the mechanism. Synthetic siRNA transcripts were developed as a versatile class of molecular tools that have a diverse range of programmable roles, being involved in the regulation of several biological processes, thereby providing the perspective of an alternative option to classical treatment. In this review, we summarize the latest information related to the application of siRNA in oral malignancy together with molecular aspects of the technology and also the perspective upon the delivery system. Also, the emergence of newer technologies such as clustered regularly interspaced short palindromic repeats/Cas9 or transcription activator-like effector nucleases in comparison with the RNAi approach is discussed in this paper. Keywords: RNA interference, oral cancer, therapeutic strategy, mechanistic and biochemical insights

Alexandra Iulia Irimie,1 Laura Sonea,2 Ancuta Jurj,3 Nikolay Mehterov,4,5 Alina Andreea Zimta,2,3 Liviuta Budisan,3 Cornelia Braicu,3 Ioana Berindan-Neagoe2,3,6 1Department of Prosthodontics and Dental Materials, Faculty of Dental Medicine, 2MedFuture Research Center for Advanced Medicine, 3Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Department of Medical Biology, Medical University of Plovdiv, 5Technological Center for Emergency Medicine, Plovdiv, Bulgaria; 6Department of Functional Genomics and Experimental Pathology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania Abstract: Oral cancer is a prevalent cancer type on a global scale, whose traditional treatment strategies have several drawbacks that could in the near future be overcome through the development of novel therapeutic and prognostic strategies. Nanotechnology provides an alternative to traditional therapy that leads to enhanced efficiency and less toxicity. Various nanosystems have been developed for the treatment of oral cancer, including polymeric, metallic, and lipid-based formulations that incorporate chemotherapeutics, natural compounds, siRNA, or other molecules. This review summarizes the main benefits of using these nanosystems, in parallel with a particular focus on the issues encountered in medical practice. These novel strategies have provided encouraging results in both in vitro and in vivo studies, but few have entered clinical trials. The use of nanosystems in oral cancer has the potential of becoming a valid therapeutic option for patients suffering from this malignancy, considering that clinical trials have already been completed and others are currently being developed. Keywords: oral cancer, nanoparticle, lipidic nanosystems, polymeric micelles, dendrimers

Cornelia Braicu,1 Roxana Cojocneanu-Petric,1,2 Sergiu Chira,1 Anamaria Truta,1,3 Alexandru Floares,4 Bogdan Petrut,5,6 Patriciu Achimas-Cadariu,7,8,* Ioana Berindan-Neagoe1,9–11,*1Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; 3Department of Medical Genetics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Solutions of Artificial Intelligence Applications, Cluj-Napoca, Romania; 5Department of Urology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 6Department of Urology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 7Department of Surgery, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 8Department of Surgical Oncology and Gynaecological Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 9Department of Immunology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 10Department of Functional Genomics and Experimental Pathology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 11Department of Experimental Therapeutics M.D. Anderson Cancer Center Houston, TX, USAAbstract: MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.Keywords: bladder cancer, miRNA, prognostic, diagnostic

Ciprian Tomuleasa,1,2,* Cornelia Braicu,1,* Alexandra Irimie,3 Lucian Craciun,1 Ioana Berindan-Neagoe1,4,51Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 2Department of Hematology, Ion Chiricuta Cancer Center, 3Department of Prosthetic Dentistry and Dental Materials, 4Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, 5Department of Functional Genomics and Experimental Pathology, the Oncological Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania*These authors contributed equally to this workAbstract: Nanoparticles have displayed considerable promise for safely delivering therapeutic agents with miscellaneous therapeutic properties. Current progress in nanotechnology has put forward, in the last few years, several therapeutic strategies that could be integrated into clinical use by using constructs for molecular diagnosis, disease detection, cytostatic drug delivery, and nanoscale immunotherapy. In the hope of bringing the concept of nanopharmacology toward a viable and feasible clinical reality in a cancer center, the present report attempts to present the grounds for the use of cell-free nanoscale structures for molecular therapy in experimental hematology and oncology.Keywords: hematological malignancies, nanoparticles, translational medicine