Cancer Genetics and Epigenetics 2024, Vol.12, No.4, 182-193 http://medscipublisher.com/index.php/cge 185 the E6 transcript in HPV16-positive cervical cancer cell lines. The results showed effective knockdown of E6 and E7 expression, leading to the accumulation of p53 and pRB proteins, and a decrease in MCM7 and p16 proteins. This resulted in a significant reduction in the proliferation and invasiveness of cervical cancer cells in vitro (Zhou et al., 2013). Another study designed a small interfering RNA (siRNA) targeting the HPV16-E7 region, which led to the degradation of both E6 and E7 mRNAs and proteins. This silencing induced the accumulation of p53 and p21, and hypophosphorylation of retinoblastoma (Rb) protein, ultimately causing massive apoptotic cell death in HPV-positive cancer cells (Sima et al., 2008). These in vitro studies underscore the efficacy of RNAi in silencing HPV oncogenes, thereby inhibiting the growth and inducing apoptosis in cervical cancer cells. The specific targeting of E6 and E7 oncogenes through RNAi not only disrupts the oncogenic pathways but also restores the function of tumor suppressor proteins, highlighting the therapeutic potential of RNAi in cervical cancer treatment. 3.2 In Vivo research In vivo studies have further validated the efficacy of RNAi in cervical cancer therapy. For example, a study involving the inoculation of monoclonal cells transduced with lentiviral-vector mediated shRNA targeting HPV16 E6/E7 into nude mice showed dramatically inhibited tumorigenesis and growth, as well as prolonged survival time of the mice (Zhou et al., 2013). Another study investigated the effect of HPV16 E6 siRNA on cervical cancer cell line CaSki cells in nude mice. The results demonstrated that siRNA administration significantly inhibited tumor growth, suppressed E6 protein expression, and induced tumor necrosis and apoptosis (Niu et al., 2006). Moreover, a study targeting E6/E7 oncogenes using siRNA in a mouse model of cervical cancer showed that siRNA sequences resulted in a significant reduction in E6/E7 mRNA levels and tumor volume. Extended treatment with siRNA nearly eradicated tumors in 70% of the animals, indicating the potent therapeutic effect of RNAi in vivo (Jonson et al., 2008). These findings collectively highlight the potential of RNAi as a therapeutic strategy for cervical cancer, with significant efficacy demonstrated in animal models. 3.3 Synergistic effects with chemotherapy Combining RNAi with traditional chemotherapy agents like cisplatin has shown promising results in enhancing the sensitivity of cervical cancer cells to treatment. Studies have indicated that RNAi targeting HPV oncogenes can sensitize cancer cells to cisplatin, thereby improving the overall therapeutic outcome. For instance, RNAi-mediated silencing of HPV16 E6/E7 oncogenes has been shown to enhance the cytotoxic effects of cisplatin in cervical cancer cells, leading to increased apoptosis and reduced cell viability (Jung et al., 2015). The synergistic effect of RNAi and cisplatin is attributed to the restoration of tumor suppressor pathways and the disruption of oncogenic signaling, which makes cancer cells more susceptible to chemotherapy-induced cell death. This combination therapy approach not only targets the viral oncogenes but also leverages the cytotoxic potential of cisplatin, offering a more effective treatment strategy for cervical cancer (Phalon et al., 2010; Jung et al., 2015). The integration of RNAi with chemotherapy holds significant promise for improving the therapeutic efficacy and overcoming resistance in cervical cancer treatment. 4 Therapeutic Targets in Cervical Cancer 4.1 HPV oncogenes E6 and E7 The human papillomavirus (HPV) oncogenes E6 and E7 play a crucial role in the development and progression of cervical cancer. These oncogenes are responsible for the degradation of tumor suppressor proteins such as p53 and retinoblastoma protein (pRb), leading to uncontrolled cell proliferation and tumorigenesis (Hoppe-Seyler et al., 2018; Yeo-Teh et al., 2018; Malla and Kamal, 2021). The persistent expression of E6 and E7 is essential for maintaining the malignant phenotype of HPV-positive cancer cells, making them attractive targets for RNA interference (RNAi) strategies. RNAi approaches, including small interfering RNA (siRNA) and short hairpin RNA (shRNA), have been shown to effectively silence E6 and E7, resulting in the reactivation of p53 and pRb pathways, induction of apoptosis, and inhibition of tumor growth (Sima et al., 2008; Zhou et al., 2013; Pal and Kundu, 2020). Additionally, novel techniques such as the CRISPR/Cas13a system have demonstrated the
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