RNAs não codificantes longos (lncRNAs) envolvidos no processo de resistência medicamentosa na leucemia mieloide crônica

Abstract

Long non-coding RNAs (lncRNAs) are a class of transcripts greater than 200 nucleotides (nc) in length that do not encode proteins but perform importante regulatory functions such as mediating the activity or localization of proteins, providing organizational structures for subcellular structures, modulating transcriptional programs and regulate the expression of miRNAs. Chronic Myeloid Leukemia (CML) BCR-ABL1 is a clonal myeloproliferative hematological malignancy derived from an abnormal pluripotent stem cell in the bone marrow. The standard and successful treatment of CML is the administration of drugs from the TKI class, however resistance mechanisms can occur and interfere with their action. Due to their involvement in several biological processes, many investigations have emerged on the deregulation of lncRNAs in CML, as they are involved in the progression of the disease and could serve as potential biomarkers and therapeutic targets in CML. This study aimed to analyze the recent literature regarding mechanisms of drug resistance in chronic myeloid leukemia involving the action of lncRNAs and classify the data obtained, facilitating their understanding. Based on the literature available in the Web of Science main collection, information was collected regarding studies published in the period from 2013 to 2023 and data regarding the described lncRNAs were classified based on their mechanisms and molecular interaction when described as associated with resistance to medications in CML. The years with the highest number of publications were 2017 and 2021 and the People's Republic of China was the country with the highest number of materials produced. Among the mechanisms and molecular interactions described in the works, lncRNAs acting as ceRNA against miRNAs were identified in the positive regulation of genes associated with resistance to imatinib in axes involving MALAT1, SNHG5, UCA1, HULC and ADORA2A-AS1 and doxorubicin in axes involving FENDRR, CCDC26, LINC01515, the axes involving MEG3 and LNC000093 were associated with the negative regulation of genes associated with imatinib resistance and HOTTIP was associated with imatinib resistance through the transcriptional suppression mechanism. Although their molecular interactions have not yet been elucidated, CCAT2, HOTAIR and NEAT1 were described as possibly associated with resistance to imatinib, while MALAT1 as a possible molecular biomarker for the occurrence and development of resistance to dasatinib. Research into molecular mechanisms that could contribute to a solution has made significant progress in recent years and it is already known that lncRNAs have a multifaceted role in the resistance of CML to chemotherapy drugs, therefore, studying them opens up potential avenues for targeted therapies, for the development of biomarkers for prognosis and response to treatment in patients with CML.