RNAs intergênicos não codificantes longos (lincRNAs) associados a mecanismos de invasão no câncer cervical: uma revisão sistemática e análise in silico.

Abstract

Introduction: Long intergenic non-coding RNAs (lincRNAs) are long non-coding transcripts that regulate gene expression through different mechanisms. lincRNAs participate in essential processes such as chromatin remodeling and the organization of cellular complexes. Their dysregulation is associated with the development and progression of cervical cancer (CC). For this reason, they have been investigated as potential biomarkers and therapeutic targets in cancer research. Objective: To summarize the main studies on lincRNAs associated with invasion mechanisms in CC through a systematic literature search and in silico analysis. Methodology: The study consisted of a systematic review registered in PROSPERO and conducted according to PRISMA guidelines. Searches were performed in PubMed, ScienceDirect, and Scopus, and the methodological quality of the studies was assessed using the JBI checklist. The characterization of lincRNAs and the prediction of their interactions and functions involved in silico analyses, including genomic identification (HGNC), prediction of chemosensitivity/chemoresistance (ncRNAdrug), and lincRNA–mRNA interaction (ENCORI). Functional analyses (GO and KEGG) were conducted using ClusterProfiler, and targets were integrated into STRING to generate the PPI network, which was later refined and visualized in Cytoscape. Results: The systematic search resulted in 26 eligible studies in which 23 lincRNAs related to CC were identified, mainly associated with invasion, proliferation, and EMT mechanisms. Among these, 17 acted in invasion, 20 in proliferation, and 6 in EMT, while only two showed an association with HPV. A total of 17 lincRNAs function as ceRNAs, and three are linked to lymph node metastasis, with one also associated with distant metastasis. In silico analyses revealed possible chemoresistance mediated by TUG1 (cisplatin) and LINC00511 (paclitaxel). The predicted interactions revealed central proteins such as HSP90AB1, RPS27A, and CAV1, which stood out as hubs in the PPI network. Functional analyses showed enrichment in pathways related to ovarian steroidogenesis, cAMP signaling, and cellular regulation processes, reinforcing the role of these lincRNAs in tumor progression and potential mechanisms of therapeutic resistance. Conclusion: These findings reinforce the potential of lincRNAs as biomarkers and therapeutic targets, considering their role in important biological processes and signaling pathways linked to tumor progression.