RNA interference: new mechanistic and biochemical insights with application in oral cancer therapy

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.

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

“…RNAi as a technique can be used to suppress mis-regulated oncogenes or oncomiRs via siRNAs, shRNAs, artificial miRNAs, anti-miRs, miRzips, sponges, ceRNAs, and artificial lnc RNAs [ 177 , 180 , 181 , 182 , 183 ]. However, their delivery in vivo has always been a concern [ 177 , 182 , 183 , 184 ]. Adenoviruses are promising in vivo delivery vectors, at least in some cases [ 185 , 186 , 187 ] and have the potential to be very useful in this regard.…”

Phenylboronic Acid-Modified Polyamidoamine Mediated the Transfection of Polo-Like Kinase-1 siRNA to Achieve an Anti-Tumor Efficacy

“…5 In the gene therapy, RNA interference holds enormous proficiency in restraining the expression of target genes through small interfering RNA (siRNA), and thus it possesses great potential in the treatment of a variety of diseases including cancers. 6 , 7 To date, the occurrence and development of malignant tumors has been illustrated to be highly associated with the abnormal expression or dysregulation of cancer-related genes. 8 For example, Polo-like kinase-1 (Plk-1) plays a crucial role in promoting the progression of cell cycle by participating in the cell division.…”

Nasal Administration of Cationic Nanoemulsions as CD73-siRNA Delivery System for Glioblastoma Treatment: a New Therapeutical Approach

“…The use of small interfering ribonucleic acid (siRNA) molecules represents a promising tool for gene expression inhibition, constituting an interesting therapeutic strategy for cancer treatment, including brain tumors [24,25]. siRNA is a mechanism exerted from a RNA double strand of approximately [19][20][21][22][23] nucleotides that triggers the cleavage of specific sequences of mRNA, resulting in inhibition of gene expression either at the translation phase, or hindering the transcription of specific genes [26][27][28]. For antitumor therapy, siRNA sequences have typically been administered locally, via intracerebral/intratumoral injections, or systemically, intravenously, using liposomal systems as nucleic acid carriers, providing an excellent therapeutic opportunity for brain tumors [24,29].…”