1. Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
2. Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
3. Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
4. Departments of Ultrasound Imaging, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
5. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
† These authors have contributed equally to this work.
* These authors jointly supervised this work.
microRNAs (miRNAs) are non-coding, endogenous, small-molecule RNAs. They are involved in cell proliferation, differentiation, apoptosis, and metabolism. Additionally, they play an essential role in the development and progression of various malignancies. Recent research has revealed that miR-18a plays an important role in cancer development. However, its role in lymphoma is not yet fully understood. In this study, we investigated the clinicopathological characteristics and potential functional roles of miR-18a in lymphomas. First, we predicted the potential downstream genes of miR-18a using miRTarBase software and subjected these downstream genes to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to determine the potential mechanisms of action of these genes. We found that these target genes were closely related to cellular senescence, the p53 signaling pathway, and other signaling pathways. From the predicted downstream target genes, ATM and p53 were selected as the target genes; their deletion in patients with lymphoma was detected using the fluorescence in situ hybridization technique. The results showed that some patients with lymphoma have a deletion of the ATM and p53 genes. In addition, the deletion rates of ATM and p53 were positively correlated with the expression of miR-18a. Next, the expression levels of miR-18a and the deletion rates of ATM and p53 were used for correlation and prognostic analyses with patient clinical information. The findings revealed a significant difference in disease-free survival (DFS) between patients with lymphoma with ATM deletion and those with a normal ATM gene expression (p < 0.001). Moreover, a significant difference in overall survival (OS) and DFS between patients with p53 deletion and those with normal p53 expression was observed (p < 0.001). The results indicate that the deletion of ATM and p53 downstream of miR-18a is closely associated with the development of lymphoma. Thus, these biomarkers may serve as key prognostic biomarkers for lymphomas.
Keywords: miR-18a, Epstein-Barr virus, Lymphoma, Genomic instability, Biomarker