Effects of siRNA-mediated suppression of HPV-11 L1 expression on the proliferation and apoptosis of vaginal epithelial cells

Abstract

Abstract. The aim of the present study was to investigate the effects of human papillomavirus (HPV) infection on the gynecological disease of vaginitis and to demonstrate how the small interfering RNA (siRNA) method may be used for HPV prevention in the clinic. Human vaginal epithelial cells were transfected with HPV-11 L1 expression vector and siRNA-HPV-11 L1 vectors and a control group was transfected with scrambled siRNA. Cell proliferation in each group was analyzed using the MTT assay and the expression of apoptosis-associated proteins was measured by western blot analysis. Compared with the control group, HPV-11 L1 mRNA and protein levels were significantly increased following transfection with the HPV-11 L1 expression vector in cells (P<0.05), but this result was significantly reversed by silencing of HPV-11 L1 (P<0.05). In addition, cell proliferation in the HPV-11 group was lower than that in the control group; however, cell proliferation was significantly increased in cells transfected with silenced L1 compared with that in the control group (P<0.05). Furthermore, silencing of HPV-11 L1 significantly decreased caspase-3 and caspase-9 expressions in cells, whereas the expression was increased in the HPV-11 L1 group (P<0.05). The present study suggested that siRNA-mediated silencing of HPV-11 L1 may have potential therapeutic applications for treating gynecological diseases associated with HPV-11 infection.

In Vitro Inhibitory Analysis of Rationally Designed siRNAs against MERS-CoV Replication in Huh7 Cells

“…Currently, therapeutic siRNAs and miRNAs are found to be some of the most promising biopharmaceuticals in commercial space as oligonucleotide-based next-generation medicines [ 16 ]. Various miRNA and siRNA-based candidate drugs are being evaluated in more than 20 clinical trials and many of them have been evaluated against different viruses including HIV [ 20 ], Flock house virus (FHV) [ 21 ], Dengue virus [ 22 ], Hepatitis C virus (HCV) [ 23 ], Influenza virus [ 24 , 25 , 26 ], Hepatitis B virus (HBV) [ 27 ], Human Papillomavirus (HPV) [ 28 ], SARS coronavirus (SARS-CoV) [ 29 ], MERS-CoV [ 30 ], and SARS-CoV-2 [ 31 , 32 ]. The potential siRNAs can be predicted and designed in silico, using a computational approach to provide filtration of potential siRNA candidates with high accuracy, target specificity, and reduced off-target effects.…”

Delivery of siRNAs against MERS-CoV in Vero and HEK-293 cells: A comparative evaluation of transfection reagents

“…The genome-wide molecular screening and bioinformatics approaches have provided a platform to predict, design, and filter the potential siRNAs, shRNA, and miRNAs against various diseases ( Levanova and Poranen, 2018 , Setten et al, 2019 ). Many siRNAs and miRNAs have been designed in silico and evaluated experimentally in more than 20 clinical trials against viral diseases like HIV, Flock house virus (FHV), DENV, HBV, HCV, HPV, Influenza, SARS-CoV, SARS-CoV-2, & MERS-CoV and shown promising results ( Fakhr et al, 2016 , Hasan et al, 2014 , Huang et al, 2017 , Idrees and Ashfaq, 2013 , Kumar et al, 2013 , Liu et al, 2017 , Nur et al, 2015 , Shahid et al, 2017 ; Sohrab et al 2021; Sohrab, Aly El-Kafrawy, et al 2020; Sohrab et al, 2018 , Taning et al, 2018 , Tsai et al, 2018 , Wang et al, 2016 , Zeng et al, 2017 ; Zhang and Lu 2020). As per the status and information, we designed this study to conduct the in-silico prediction, designing, and experimental evaluation of potential siRNAs at 5 and 10nM concentrations by using two different transfection reagents in Vero and HEK-293-T cell lines.…”

In silico prediction and experimental validation of siRNAs targeting ORF1ab of MERS-CoV in Vero cell line

“…As all siRNAs are not equally potent, various rules have been suggested for the computational prediction, designing, and selection of potential siRNAs. Currently, the siRNA approach has been implemented to inhibit viral replication in cell culture against many viruses like HIV ( Liu et al, 2017 ), Flock house virus (FHV) ( Taning et al, 2018 ), Dengue virus ( Idrees and Ashfaq, 2013 ), Hepatitis C virus (HCV) ( Shahid et al, 2017 ), Influenza virus ( Huang et al, 2017 , Tsai et al, 2018 ), Hepatitis B virus (HBV) ( Wang et al, 2016 ), Human Papillomavirus (HPV) ( Zeng et al, 2017 ) and SARS coronavirus (SARS-CoV) ( Kumar et al, 2013 ).…”