Department of Oncology, Affiliated Aoyang Hospital of Jiangsu University, Jiangsu, China.
Department of Oncology, Affiliated Aoyang Hospital of Jiangsu University, Jiangsu, China.
Adv Med Sci. 2023 Sep;68(2):426-432. doi: 10.1016/j.advms.2023.10.003. Epub 2023 Oct 20.
Lung cancer (LC) is a common malignancy worldwide. A great number of circular RNAs (circRNAs) have been identified that serve crucial roles in cancer development. Extracellular vesicles (EVs) and their contents have been shown to be biomarkers for the diagnosis and prognosis of LC. Thus, we intended to clarify the functional role of EVs-derived circRNA homology domain interacting protein kinase 3 (EVs-circHIPK3) and its underlying mechanism of action.
Bioinformatics analysis was performed to validate the potential of partially circulating HIPK3 in LC diagnosis. EVs were isolated by polyethylene glycol (PEG) precipitation from plasma of 52 LC patients and 30 healthy controls. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to evaluate the expressions of candidate circRNAs (circHIPK3) and microRNA-637 (miR-637, a target of circHIPK3).
CircHIPK3 is significantly up-regulated in LC, while miR-637 expression is significantly reduced (p < 0.05). Receiver operating characteristic (ROC) curve analysis, based on the expression of EVs-circHIPK3, allowed us to distinguish LC from healthy controls (area under the curve, AUC 0.897).
Taken together, our study shows that EV-derived circHIPK3 can serve as a promising biomarker for LC patient diagnosis. However, the downstream mRNA of the circHIPK3/miR-637 axis requires further exploration to enrich our understanding of circHIPK3's mechanism in LC.
肺癌（LC）是一种常见的恶性肿瘤。已经发现了大量的环状 RNA（circRNA），它们在癌症发展中发挥着关键作用。细胞外囊泡（EVs）及其内容物已被证明是 LC 诊断和预后的生物标志物。因此，我们旨在阐明 EVs 衍生的环状同源域相互作用蛋白激酶 3（EVs-circHIPK3）的功能作用及其潜在的作用机制。
通过生物信息学分析验证了部分循环 HIPK3 在 LC 诊断中的潜在作用。从 52 例 LC 患者和 30 例健康对照者的血浆中通过聚乙二醇（PEG）沉淀法分离 EVs。采用定量逆转录-聚合酶链反应（qRT-PCR）评估候选环状 RNA（circHIPK3）和 microRNA-637（miR-637，circHIPK3 的靶标）的表达。
LC 中 circHIPK3 的表达显著上调，而 miR-637 的表达显著降低（p 均<0.05）。基于 EVs-circHIPK3 表达的受试者工作特征（ROC）曲线分析，使我们能够将 LC 与健康对照者区分开来（曲线下面积，AUC 为 0.897）。
综上所述，我们的研究表明 EV 衍生的 circHIPK3 可作为 LC 患者诊断的有前途的生物标志物。然而，circHIPK3/miR-637 轴的下游 mRNA 需要进一步探索，以丰富我们对 circHIPK3 在 LC 中的作用机制的理解。
