Shi Lin, Huang Yuanyuan, Chen Shaobing, Wang Siyun, Yan Chenxin, Chen Xiaofei, Zhang Bei, Ke Bin
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Ann Transl Med. 2023 Mar 15;11(5):215. doi: 10.21037/atm-23-178.
Circular RNA (circRNA), a unique RNA molecule with a circular structure, is relevant to the process of non-small cell lung cancer (NSCLC). However, the role and possible mechanisms of circ_0003028 in NSCLC are not completely clear. Here, we investigated the role of circ_0003028 in NSCLC progression.
We first confirmed the stability and head-to-tail junction sequences of circ_000302. Circ_0003028 expression was identified with quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC tissues, and the survival probability and prognosis were analyzed using Kaplan-Meier survival and receiver operating characteristic (ROC) analyses. Functionally, the proliferation, apoptosis, and glycolytic capacity were examined using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, a flow cytometer, commercial kits [glucose, lactate, and adenosine triphosphate (ATP)], and a Seahorse XF extracellular flux analyzer. Moreover, the potential microRNAs (miRNAs) of circ_0003028 were predicted and identified, and the target gene of miRNA (miR)-1322 and miR-1305 were also screened using DIANA-microT and TargetScan.
We first determined the head-to-tail junction sequences of circ_0003028 and its stability. Circ_0003028 was also confirmed to be upregulated in NSCLC tissues. Meanwhile, circ_0003028 had poor overall survival and high diagnostic potential in NSCLC patients. Furthermore, we found that overexpression of circ_0003028 could increase the proliferation and glycolytic capacity and restrain the apoptosis of NSCLC cells, and circ_0003028 silencing played the opposite role to circ_0003028 overexpression. Moreover, circ_0003028 might regulate miR-1305 and miR-1322, which might further regulate solute carrier family 5 member 1 (SLC5A1).
Circ_0003028 could accelerate the malignant behaviors and glycolytic capacity of NSCLC cells via a mechanism that may be related to miR-1305 or the miR-1322/SLC5A1 axis. Therefore, the findings of the current study provide a preliminary theoretical basis for NSCLC therapy and diagnosis.
环状RNA(circRNA)是一种具有环状结构的独特RNA分子,与非小细胞肺癌(NSCLC)的发生发展过程相关。然而,circ_0003028在NSCLC中的作用及可能机制尚不完全清楚。在此,我们研究了circ_0003028在NSCLC进展中的作用。
我们首先确认了circ_0003028的稳定性及其头对头连接序列。采用定量逆转录聚合酶链反应(qRT-PCR)检测NSCLC组织中circ_0003028的表达,并通过Kaplan-Meier生存分析和受试者工作特征(ROC)分析评估生存概率和预后。在功能方面,使用细胞计数试剂盒-8(CCK-8)、5-乙炔基-2'-脱氧尿苷(EdU)染色、流式细胞仪、商业试剂盒[葡萄糖、乳酸和三磷酸腺苷(ATP)]以及Seahorse XF细胞外通量分析仪检测细胞增殖、凋亡和糖酵解能力。此外,预测并鉴定了circ_0003028潜在的微小RNA(miRNA),并使用DIANA-microT和TargetScan筛选了miR-1322和miR-1305的靶基因。
我们首先确定了circ_0003028的头对头连接序列及其稳定性。还证实circ_0003028在NSCLC组织中上调。同时,circ_0003028在NSCLC患者中的总生存期较差且具有较高的诊断潜力。此外,我们发现circ_0003028的过表达可增加NSCLC细胞的增殖和糖酵解能力并抑制其凋亡,而circ_0003028沉默则发挥与circ_0003028过表达相反的作用。此外,circ_0003028可能调控miR-1305和miR-1322,而这两者可能进一步调控溶质载体家族5成员1(SLC5A1)。
circ_0003028可能通过与miR-1305或miR-1322/SLC5A1轴相关的机制加速NSCLC细胞的恶性行为和糖酵解能力。因此,本研究结果为NSCLC的治疗和诊断提供了初步的理论依据。