Role of lncRNA Alterations in Cervical Oncogenesis

Abstract

DOI: 10.14744/ejmo.2022.74937 EJMO 2022;6(2):111–120 Cite This Article: de Oliveira AL, de Almeida VD, Pereira TP, Carvalho AE, Nogueira Wojcieszyn VS, Andrade MF, et al. Role of lncRNA Alterations in Cervical Oncogenesis. EJMO 2022;6(2):111–120. Address for correspondence: Valéria Duarte de Almeida, MD. Departamento de Ciências Biomédicas, Faculdade de Ciências da Saúde da Universidade do Estado do Rio Grande do Norte, R. Atirador Miguel Antonio da Silva, S/n, Aeroporto, Mossoró RN, 59607-360, Brazil Phone: +5584 9 9609-0711 E-mail: valeriaalmeida@alu.uern.br Submitted Date: December 30, 2021 Accepted Date: May 26, 2022 Available Online Date: June 06, 2022 ©Copyright 2020 by Eurasian Journal of Medicine and Oncology Available online at www.ejmo.org OPEN ACCESS This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Review 112 Lopes de Oliveira. et al., Role of lncRNA Alterations in Cervical Oncogenesis / doi: 10.14744/ejmo.2022.74937 Viral oncogenes E6 and E7 are consistently overexpressed after HPV genome incorporation into host cell DNA. Its incorporation leads to a series of oncogenic advances. The best-studied and known advances are induction of tumor suppressor protein p53 degradation by the viral oncoprotein E6 and cellular transformation through interaction with the PDZ domain of cellular proteins and pRb led by oncoprotein E7. The HPV16 E6/E7 proteins can also increase the expression of the polycomb repressive complex 2 (PRC2) and the methyltransferase enhancer of zeste homolog 2 (EZH2) at the level of messenger RNA (mRNA) and protein, which modify gene expression through increased histone H3 Lys27 trimethylation.[8,10,12,13] Recent studies have associated changes in expression levels of non-coding RNA molecules, such as long non-coding RNAs (lncRNAs), induced by HPV as another possible pathogenic pathway important for neoplastic process development.[14,15] Long non-coding RNAs (lncRNAs) are a class of ribonucleic acid (RNA) molecules with more than 200 nucleotides in length that do not encode proteins. They play important roles in several cellular activity regulations, such as epigenetic regulation, silencing of chromosomes, chromatin modification, transcriptional activation, post-transcriptional regulation, protein regulation, and can be used as “sponges” competitively inhibiting microRNAs (miRNAs). [7,16-18] Growing evidence has established the potential relationship between dysregulation of lncRNA expression and numerous human diseases such as cancer, metabolic diseases, neurodegenerative and psychiatric diseases, and immune dysfunction.[18-22] Numerous studies show that they play vital roles in the progression and development of various human neoplasms. The expression of lncRNAs is different in distinct tissues, and its expression may be increased or reduced. lncRNAs dysfunction is involved in tumorigenesis, from proliferation to resistance to apoptosis, angiogenesis, and metastasis. They can act as important biomarkers and potential drug targets for various types of cancer, and the regulation of lncRNA expression can influence tumor development and progression.[7,8,21,23-25] Changes in the expressiveness of lncRNAs are associated with the emergence, progression, and prognosis of different types of cancer, including cervical cancer.[7,8,10] Also, HPV can compromise the expressiveness rates of different types of lncRNAs, with biological consequences in the onset, progression, and prognosis of cervical cancer.[9] Therefore, this study aimed to carry out a survey, through a review of specialized literature, the contribution of lncRNAs with altered expression levels with the "Hallmarks" of cervical cancer, through the analysis of mechanisms of action promoted by varying levels of expressiveness in the pathogenesis of cervical cancer, verifying the biological significance of expression in the onset, progression, and prognosis of the disease.