The Autophagy Process in Cervical Carcinogenesis: Role of Non-Coding-RNAs, Molecular Mechanisms, and Therapeutic Targets

Cells. 2022 Apr 13;11(8):1323. doi: 10.3390/cells11081323.

Abstract

Autophagy is a highly conserved multistep lysosomal degradation process in which cellular components are localized to autophagosomes, which subsequently fuse with lysosomes to degrade the sequestered contents. Autophagy serves to maintain cellular homeostasis. There is a close relationship between autophagy and tumor progression, which provides opportunities for the development of anticancer therapeutics that target the autophagy pathway. In this review, we analyze the effects of human papillomavirus (HPV) E5, E6, and E7 oncoproteins on autophagy processes in cervical cancer development. Inhibition of the expression or the activity of E5, E6, and E7 can induce autophagy in cells expressing HPV oncogenes. Thus, E5, E6, and E7 oncoproteins target autophagy during HPV-associated carcinogenesis. Furthermore, noncoding RNA (ncRNA) expression profiling in cervical cancer has allowed the identification of autophagy-related ncRNAs associated with HPV. Autophagy-related genes are essential drivers of autophagy and are regulated by ncRNAs. We review the existing evidence regarding the role of autophagy-related proteins, the function of HPV E5, E6, and E7 oncoproteins, and the effects of noncoding RNA on autophagy regulation in the setting of cervical carcinogenesis. By characterizing the mechanisms behind the dysregulation of these critical factors and their impact on host cell autophagy, we advance understanding of the relationship between autophagy and progression from HPV infection to cervical cancer, and highlight pathways that can be targeted in preventive and therapeutic strategies against cervical cancer.

Keywords: E6; E7; HPV E5; autophagy; cervical cancer; ncRNAs; signaling pathways.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics
  • Carcinogenesis / genetics
  • Female
  • Humans
  • Oncogene Proteins, Viral* / metabolism
  • Papillomaviridae / genetics
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections* / genetics
  • Papillomavirus Infections* / pathology
  • RNA, Untranslated / genetics
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • RNA, Untranslated