Yüksel Tuğba Nurcan, Bozgeyik Esra, Bozgeyik İbrahim
Department of Pharmacology, Tekirdağ Namik Kemal University Faculty of Medicine, Tekirdağ, Turkey.
Department of Medical Services and Techniques, Adiyaman University Vocational School of Health Sciences, Adiyaman, Turkey.
Eurasian J Med. 2023 Oct;55(3):204-207. doi: 10.5152/eurasianjmed.2023.23073.
ADP-ribosylation factor-like tumor suppressor gene 1 is a member of the Ras superfamily of small guanosine triphosphatases that are known to be involved in multiple regulatory pathways in the multistage development of human cancers. Also, ADP-ribosylation factor-like tumor suppressor gene 1 expression levels have been reported to be dramatically lower in both cancer cell lines and tumor tissues compared to controls. Accordingly, defects in the regulation of the ADP-ribosylation factor-like tumor suppressor gene 1 gene seems have key tumor suppressive effects in the formation and development of human cancers including lung cancer. Moreover, microRNAs regulating the expression of ADP-ribosylation factor-like tumor suppressor gene 1 have not been described previously. Accordingly, the present study aimed to reveal the influence of miR-16-5p on the regulation of ADP-ribosylation factor-like tumor suppressor gene 1 gene.
A549 lung adenocarcinoma cells were used. For the overexpression and silencing experiments of miR-16-5p synthetic microRNA mimics and inhibitors were used, respectively. Gene expression analyses were achieved with the help of quantitative real-time polymerase chain reaction.
MiR-16-5p was identified to be predictive target of ADP-ribosylation factor-like tumor suppressor gene 1 and directly targets the expression of ADP-ribosylation factor-like tumor suppressor gene 1 as revealed by the overexpression and silencing experiments. Specifically, it was found that miR-16-5p-overexpressed A549 cells showed a decrease in ADP-ribosylation factor-like tumor suppressor gene 1 gene expression, whereas miR16-5p-suppressed cells showed an increase in expression. These findings possibly suggest that miR-16-5p is the direct regulatory microRNA that posttranscriptionally regulates the expression of ADP-ribosylation factor-like tumor suppressor gene 1.
Collectively, miR-16-5p seems to be a key regulatory molecule involved in the posttranscriptional regulation of the ADP-ribosylation factor-like tumor suppressor gene 1, and it might be responsible for the downregulation of this gene in lung cancer.
ADP核糖基化因子样肿瘤抑制基因1是小GTP酶Ras超家族的成员，已知其参与人类癌症多阶段发展中的多种调控途径。此外，据报道，与对照组相比，ADP核糖基化因子样肿瘤抑制基因1在癌细胞系和肿瘤组织中的表达水平均显著降低。因此，ADP核糖基化因子样肿瘤抑制基因1的调控缺陷似乎在包括肺癌在内的人类癌症的形成和发展中具有关键的肿瘤抑制作用。此外，此前尚未描述过调控ADP核糖基化因子样肿瘤抑制基因1表达的微小RNA。因此，本研究旨在揭示miR-16-5p对ADP核糖基化因子样肿瘤抑制基因1调控的影响。
使用A549肺腺癌细胞。分别使用miR-16-5p合成微小RNA模拟物和抑制剂进行过表达和沉默实验。借助定量实时聚合酶链反应进行基因表达分析。
miR-16-5p被鉴定为ADP核糖基化因子样肿瘤抑制基因1的预测靶点，过表达和沉默实验表明其直接靶向ADP核糖基化因子样肿瘤抑制基因1的表达。具体而言，发现miR-16-5p过表达的A549细胞中ADP核糖基化因子样肿瘤抑制基因1的基因表达降低，而miR-16-5p抑制的细胞中表达增加。这些发现可能表明miR-16-5p是直接调控微小RNA，在转录后水平调控ADP核糖基化因子样肿瘤抑制基因1的表达。
总体而言，miR-16-5p似乎是参与ADP核糖基化因子样肿瘤抑制基因1转录后调控的关键调控分子，可能是肺癌中该基因下调的原因。
