Zhou Hao, He Yuxiang, Ou Chunlin, He Xiaoyun, Cao Pengfei
Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
J Cancer. 2023 May 8;14(8):1301-1308. doi: 10.7150/jca.83854. eCollection 2023.
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 hybridization technique. The results showed that some patients with lymphoma have a deletion of the and genes. In addition, the deletion rates of and were positively correlated with the expression of miR-18a. Next, the expression levels of miR-18a and the deletion rates of and 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 deletion and those with a normal gene expression ( < 0.001). Moreover, a significant difference in overall survival (OS) and DFS between patients with deletion and those with normal expression was observed ( < 0.001). The results indicate that the deletion of and downstream of miR-18a is closely associated with the development of lymphoma. Thus, these biomarkers may serve as key prognostic biomarkers for lymphomas.
微小RNA（miRNA）是一类非编码的内源性小分子RNA。它们参与细胞增殖、分化、凋亡及代谢过程。此外，它们在多种恶性肿瘤的发生发展中发挥着重要作用。近期研究表明，miR-18a在癌症发展中起重要作用。然而，其在淋巴瘤中的作用尚未完全明确。在本研究中，我们调查了miR-18a在淋巴瘤中的临床病理特征及潜在功能作用。首先，我们使用miRTarBase软件预测miR-18a的潜在下游基因，并对这些下游基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，以确定这些基因的潜在作用机制。我们发现这些靶基因与细胞衰老、p53信号通路及其他信号通路密切相关。从预测的下游靶基因中，选择ATM和p53作为靶基因；采用荧光杂交技术检测淋巴瘤患者中它们的缺失情况。结果显示，部分淋巴瘤患者存在 和 基因的缺失。此外， 和 的缺失率与miR-18a的表达呈正相关。接下来，将miR-18a的表达水平以及 和 的缺失率与患者临床信息进行相关性和预后分析。结果显示， 基因缺失的淋巴瘤患者与 基因表达正常的患者在无病生存期（DFS）方面存在显著差异（<0.001）。此外， 基因缺失的患者与 表达正常的患者在总生存期（OS）和DFS方面也存在显著差异（<0.001）。结果表明，miR-18a下游的 和 的缺失与淋巴瘤的发生密切相关。因此，这些生物标志物可能作为淋巴瘤的关键预后生物标志物。
