Autophagy-HPV-DNA Methylation modifications; A chain for Cervical Cancer pathogenesis

One of the critical elements during tumorigenesis is the environmental factors. Environmental factors next to the host-associated factors lead to the catastrophe. HPV E۶ and E۷ proteins in CC (Cervical Cancer) are well studied. Meanwhile, the virus can induce some deeper effects, which could be key to improving our understanding of CC pathogenesis. In the current review, we tried to highlight the association between autophagy-HPV-DNA methylation modifications during CC pathogenesis. This could provide a view of the molecular mechanisms and perspective for future research. Methods: All relevant literature was searched in electronic databases by using Cervical Cancer, Autophagy, DNA Methylation, and Human Papilloma Virus as keywords. the search was performed in PubMed, Web of Science, and Google Scholar by search data filter from ۲۰۲۰ to September ۲۰, ۲۰۲۴. All literature was listed in EndNote and screamed based on inclusion criteria (English literature, original research, relevant to study topics). Results: Search results led to more than ۸۰۰ documents and after duplicate removal and screening ۹ documents were included. by reviewing all relevant documents based on the aim of the current study major findings are listed here. Autophagic flux is a critical element during infections and cell damage. Current studies provide a body of knowledge about alterations in autophagy during CC. Some of these changes seem to be due to the HPV infection. For instance, it has been shown that HPV۱۶ alters autophagy by interacting with proteins, Beclin-۱ and LC۳B, which are necessary for forming and degrading autophagosomes. Also, other important proteins affected by HPV E۶ and E۷ include UBC۹, which upsets the process of autophagic cells by stopping the fusion of autophagic vacuoles with lysosomes. In addition, several important genes associated with autophagosome formation, such as ATG۹B and LAMP۱, were found to be downregulated in CC. This downregulation occurs when the oncogenic proteins E۶ and E۷ are reduced, negatively affecting autophagy and led to less cell proliferation and tumor growth in CC. Studies have shown that miR-۱۹-۳p targets PTEN, it can stop autophagy and help cancer cells to survive and spread. Another critical element during CC pathogenesis is DNA Methylation. This DNA Methylation can alter the autophagic flux in CC. Ren et al. showed that TET۱ was significantly decreased in cervical cancer cells. TET۱ inhibition was shown to enhance autophagy by regulating the methylation of autophagy promoter regions, such as NKRF and HIST۱H۲AK. This regulation shows the importance of DNA methylation in autophagy and it can affect the growth of CC. Conclusion: There seems to be a tight association between Autophagy and HPV infection. This association is also conceded to the DNA Methylation modifications. In both, the autophagy is the main pathway. There are critical gaps in knowledge about autophagy and its elements in CC which need to be addressed in future research. Major limitation in our current study and this field is the limited number of primary literatures.

کلیدواژه ها:

Cervical Cancer ، Autophagy ، DNA Methylation ، Human Papilloma Virus