Cancer Genetics and Epigenetics 2024, Vol.12, No.4, 182-193 http://medscipublisher.com/index.php/cge 184 Figure 1 Mechanisms of MicroRNA (miRNA) and Small Interfering RNA (siRNA) (Adapted from Zhang et al., 2023) Image Caption: miRNA is transcribed from genes and processed by Drosha and DGCR8 into pre-miRNA, which is then transported to the cytoplasm by Exportin 5. After further processing by Dicer, miRNA binds to the RISC complex and leads to mRNA degradation or translation inhibition through partial complementary pairing with the target mRNA. siRNA, on the other hand, originates from a double-stranded RNA (dsRNA) precursor. It is cleaved by Dicer to form siRNA fragments, which bind to RISC and directly cleave the target mRNA, thereby inhibiting the expression of the target protein (Adapted from Zhang et al., 2023) 2.3 Advantages and challenges RNAi offers several advantages over traditional cancer therapies. One of the primary benefits is its high specificity and efficiency in gene silencing. RNAi can target virtually any gene with a known sequence, allowing for the selective knockdown of disease-related genes without affecting other genes (Agrawal et al., 2003; Leung and Whittaker, 2005). This specificity reduces the likelihood of off-target effects and minimizes damage to healthy cells, which is a significant limitation of conventional chemotherapy and radiation therapy. Additionally, RNAi can be used to target genes that are otherwise considered "undruggable" by small molecules or antibodies, expanding the range of potential therapeutic targets (Takeshita and Ochiya, 2006; Hu et al., 2020). However, there are several challenges associated with RNAi-based therapies. One of the main obstacles is the delivery of siRNAs to target cells in vivo. siRNAs are susceptible to degradation by nucleases in the bloodstream and may elicit immune responses. Effective delivery systems, such as nanoparticles and viral vectors, are being developed to protect siRNAs from degradation and facilitate their uptake by target cells (Chalbatani et al., 2019; Hu et al., 2020). Another challenge is the potential for off-target effects, where siRNAs may inadvertently silence genes with partial sequence homology. Advances in siRNA design and chemical modifications are being made to enhance specificity and reduce off-target effects (Senapati et al., 2019; Zhang et al., 2023). Despite these challenges, the therapeutic potential of RNAi in cancer therapy remains promising, with ongoing research focused on overcoming these hurdles to bring RNAi-based treatments to clinical practice. 3 Current Research on RNAi in Cervical Cancer 3.1 Preclinical studies Recent preclinical studies have demonstrated the potential of RNA interference (RNAi) in targeting HPV oncogenes, particularly E6 and E7, which are crucial for the pathogenesis and progression of cervical cancer. For instance, a study utilized lentiviral-vector mediated shRNA to target the common promoter of HPV16 E6/E7 and
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==