Cancer Genetics and Epigenetics 2024, Vol.12, No.4, 182-193 http://medscipublisher.com/index.php/cge 183 can induce apoptosis in cervical carcinoma cells and inhibit tumor growth, offering a targeted approach that could complement existing therapies (Milner, 2003; DiPaolo and Alvarez-Salas, 2004). Moreover, the adaptability of RNAi to genetic variations within the viral genome enhances its potential as a versatile and effective treatment modality (Milner, 2003). This study evaluated the current status of RNAi-based therapies for cervical cancer, assessed their efficacy in preclinical and clinical settings, and identified the challenges and future directions for integrating RNAi into standard treatment protocols. By synthesizing the latest research findings, this study provides a comprehensive overview of the potential of RNAi in cervical cancer treatment and emphasizes its role in advancing personalized medicine to address this prevalent and deadly disease. 2 Mechanisms of RNAi in Cancer Therapy 2.1 Biogenesis of RNAi RNA interference (RNAi) is a biological process where double-stranded RNA (dsRNA) induces the silencing of specific genes. The biogenesis of RNAi begins with the introduction of dsRNA into the cell, which is then processed by an RNase III-like enzyme called Dicer. Dicer cleaves the dsRNA into small interfering RNAs (siRNAs) that are typically 21-25 nucleotides in length (Elbashir et al., 2001; Agrawal et al., 2003). These siRNAs are then incorporated into the RNA-induced silencing complex (RISC), where they guide the complex to complementary messenger RNA (mRNA) targets. The RISC, with the help of Argonaute proteins, cleaves the target mRNA, leading to its degradation and subsequent gene silencing (Agrawal et al., 2003; Leung and Whittaker, 2005). MicroRNAs (miRNAs) are another class of small RNAs involved in RNAi. They are transcribed as primary miRNAs (pri-miRNAs) and processed in the nucleus by the Drosha-DGCR8 complex into precursor miRNAs (pre-miRNAs). These pre-miRNAs are then exported to the cytoplasm and further processed by Dicer into mature miRNAs. The mature miRNAs are incorporated into RISC, where they typically bind to the 3' untranslated region (UTR) of target mRNAs, leading to translational repression or mRNA degradation (Agrawal et al., 2003; Leung and Whittaker, 2005). The biogenesis and function of miRNAs closely resemble those of siRNAs, highlighting the conserved nature of the RNAi pathway across different organisms. 2.2 RNAi-mediated gene silencing RNAi-mediated gene silencing involves the use of siRNAs and miRNAs to target and degrade specific mRNAs, thereby reducing the expression of the corresponding genes. siRNAs are exogenously introduced or endogenously processed from long dsRNAs. Once incorporated into RISC, the siRNA guides the complex to the complementary mRNA, where the Argonaute protein within RISC cleaves the mRNA, leading to its degradation and preventing translation (Elbashir et al., 2001; Leung and Whittaker, 2005). This mechanism is highly specific, as the siRNA sequence must perfectly match the target mRNA sequence for effective silencing. miRNAs, on the other hand, are endogenously encoded and processed from primary transcripts. They typically bind to partially complementary sequences in the 3' UTR of target mRNAs, leading to translational repression or mRNA degradation. The degree of complementarity between the miRNA and its target mRNA determines the mode of silencing; perfect or near-perfect complementarity results in mRNA cleavage, while partial complementarity leads to translational repression (Agrawal et al., 2003; Leung and Whittaker, 2005). Both siRNAs and miRNAs play crucial roles in regulating gene expression and have been harnessed for therapeutic purposes, particularly in cancer therapy, where they can be used to silence oncogenes or other genes involved in tumor progression (Figure 1) (Chalbatani et al., 2019; Zhang et al., 2023). Zhang et al. (2023) summarized the distinct pathways of miRNA and siRNA, both of which play critical roles in gene expression regulation. miRNA regulates the expression of multiple genes through partial complementary pairing, while siRNA induces mRNA cleavage via precise complementarity. Understanding these molecular mechanisms is crucial for the development of new gene therapies and drug targeting techniques.
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