Identificação de RNAs longos não codificantes associados com a resistência e sensibilidade â quimioterapia em câncer do colo do útero: uma análise in silico e Revisão Sistemática da Literatura

Abstract

Cervical cancer (CC) represents a global challenge, with alarming predictions of increased incidence and mortality by 2030. Its treatment can involve surgery, radiotherapy, and chemotherapy, but the effectiveness can be compromised by the resistance of cancer cells to chemotherapeutic agents. To improve treatments, it is crucial to understand the molecular processes of carcinogenesis and cellular responses to drugs. One notable mechanism involves long non-coding RNAs (lncRNAs), which can act as biomarkers. In this context, the study aimed to identify lncRNAs associated with chemotherapy resistance and sensitivity in CC. The methodology followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, with searches conducted in databases such as PubMed, Science Direct, and Web of Science, resulting in the selection of 21 articles published between 2017 and 2023, written in English. To identify the target genes of microRNAs, the online tools miRTargetlink and DIANA Tools were used. The results highlighted MEG3 as sensitive to cisplatin (DDP) and identified 18 lncRNAs implicated in resistance to three chemotherapeutic agents, including DDP, among which GAS5 is included, which were the subject of further studies. Additionally, these lncRNAs are involved in resistance to paclitaxel (PTX), 5-fluorouracil (5-Fu), and doxorubicin (DTX). In silico analyses revealed that the miRNAs regulated by these lncRNAs target 40 genes, including HMGB1 and STAT3. These genes play critical roles in biological processes related to cancer development, progression, and treatment response, being involved in important carcinogenesis pathways such as proteoglycan pathways, p53 signaling, and the PI3K-Akt pathway. These findings underline the importance of lncRNAs as potential markers of treatment response and suggest that the regulation of miRNAs can directly influence biological pathways frequently dysregulated in cancer