Investigating the role of CYP2W1 in cancer progression

Date

2023-12-21

Author

Akkulak, Merve

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CYP2W1 is a newly discovered oncofetal gene which specifically expressed in colon and hepatocellular carcinomas and expression rates are directly proportional to the severity of these diseases. Although cancer-specific expression makes it an ideal target for cancer therapies, its potential role in cancer remains unknown. The aim of this research is to determine its precise biological involvement in cancer progression. For this reason, the CYP2W1 gene was silenced in a HepG2 human hepatocarcinoma cell line using an RNAi gene repression approach, and then common mechanisms in cancer and embryogenesis including cell proliferation, apoptosis, invasion, Epithelial-Mesenchymal Transition (EMT) and angiogenesis were investigated. Our results revealed that silencing the CYP2W1 gene resulted in a reduction in HepG2 cell viability. However, the suppression of CYP2W1 expression did not have a statistically significant effect on apoptosis, cell invasion, or the mRNA and protein expression levels of EMT markers in general, but only β-catenin mRNA expression was significantly reduced. In addition, silencing of CYP2W1 reduced the VEGF-A gene expression and secretion, but the expected functional effects of it on in vitro angiogenesis were not observed. In contrast to our hypotheses based on clinical studies, the expression of CYP2W1 did not exhibit a statistically significant impact on the stages of cancer progression in HepG2 cells. In addition, the effects of hesperidin-treated Lacticaseibacillus rhamnosus GG (LGG) cell-free supernatants on Caco-2 colon cancer cell viability and CYP2W1 gene expression were investigated during this study since plant polyphenols and their metabolites as microbial by-products of the gut microbiome might be a crucial factor in CYP2W1 regulation during colon cancer. It is found that cell-free supernatants derived from LGG bacteria reduced CYP2W1 gene expressions and cell proliferation of the Caco 2 human colon cancer cell line. So far, studies have focused on the fact that CYP2W1 gene overexpression might be associated with cancer progression. However, the findings of this study suggested that microbial dysfunction might influence the progression of colon cancer by altering CYP2W1 gene expression, or such alterations in colon cancer might result in the modulation of CYP2W1 expression. To our knowledge, this is the first study that explores the role of CYP2W1 in the key stages of cancer progression with RNAi-mediated gene silencing strategy. In conclusion, this study can open up new perspectives for researchers to investigate the direct effect of the CYP2W1 gene on cancer as well as the potential factors that regulate this gene.

Subject Keywords

CYP2W1, Cancer, siRNA, Lacticaseibacillus rhamnosus GG, Cell-free Supernatant

URI

https://hdl.handle.net/11511/107810

Collections

Graduate School of Natural and Applied Sciences, Thesis