Transcriptional Regulation of Epithelial to Mesenchymal Transition Related Genes by Lipopolysaccharide in Human Cervical Cancer Cell Line HeLa

Abstract

Objective: Cancer is one of the common diseases in the world, and cervical cancer is the fourth one. In this type of cancer, many risk factors, especially infectious diseases, such as human papilloma virus (HPV) and gram-negative bacteria can have important effects on the expression of epithelial to mesenchymal transition related genes like Snail, E-cadherin, and ZEB-1, responsible for connecting cell tissues. In this study, we have investigated the effect of Escherichia coli O111:B4 Lipopolysaccharide (LPS) on HPV positive cell line (HeLa), the expression level of the (Snail, E-cadherin, and ZEB-1), HPV oncogenes (E6, E7) and also microRNA-9, 192. Materials and Methods: HeLa cell line was treated with LPS to analyze Snail, E-cadherin, ZEB-1, E6, E7 and also microRNA-9, 192 expression by quantitative real-time PCR in 24, 48 and 72 hours. Results: Quantitative real-time PCR revealed a significant reduction in E-cadherin mRNA level at 10ug/L of LPS in three time-points and after 24 hours at 5ug/L of LPS; however, ZEB-1 at 10ug/L of LPS and Snail at 5, 10ug/L of LPS are up-regulated. E7 also illustrated a slight increase, but we did not find any relationship between E7 and LPS treatment. Additionally, there are upward trends in microRNA-9, 192 levels. Conclusion: The result of this study, LPS is able to reduce E-cadherin expression, caused by increase in repressor E-cadherin protein expression and some microRNAs, probably. Since bacterial infection can be in cervical site, it is likely to be effective in reducing the E-cadherin expression in the EMT and enhance cancer process, therefore; removing these infections by using the appropriate antibiotics may result in slowing down this process, which requires more research.

Slug Is A Surrogate Marker of Epithelial to Mesenchymal Transition (EMT) in Head and Neck Cancer

“…The inverse correlation between Slug and p16 positivity, as a marker for human papilloma virus (HPV) infection, requires adjustment for p16 effects when examining the clinical effects of Slug expression ( p = 0.012). There are several studies in HPV positive cervical cancer cells (especially HeLa cells) that report that the HPV related oncogenes E6 and E7 might repress E-cadherin expression independent of Slug and consequently induce EMT in cervical cancer [ 50 , 51 , 52 , 53 , 54 ]. In HNC the association between HPV status and EMT is even less known, but the results also support a positive association between HPV status and EMT in vitro [ 55 ].…”

E-cadherin, Snail, ZEB-1, DNMT1, DNMT3A and DNMT3B expression in normal and breast cancer tissues*

“…Multiple lines of evidence confirmed that various genes, such as E-cadherin, Snail, and ZEB-1 are known as EMT-related genes. It has been shown that deregulation of these genes is associated with metastasis and other cancer -related processes (Tavakolian et al, 2019;Brabletz et al, 2018). In a study, Chen et al, indicated that expression of E-cadherin is associated with the metastasized lymph node (Chen et al, 2015).…”

Evaluating the expression level of HERV-K env, np9, rec and gag in breast tissue

“…Another HERV-associated gene whose its expression was elevated in malignant tissues was HERV-k np9 . There are several reports claiming that the expression level of this gene is increased in a variety of human cancers, ranging from solid tumors, such as breast cancer [25, 29] and melanoma [30], to chronic hematologic malignancies [31]. The oncogenic property of np9 is also evident in transformed cell lines, where it has been reported that this gene could serve as a growth factor for cancer cells [32].…”