环状RNA（circRNA）已被证明在肿瘤发展中发挥着关键作用。本研究旨在探讨circMBOAT2在非小细胞肺癌（NSCLC）中的调控机制及其与慢性应激诱导的肿瘤生长的关系。我们构建了 circMBOAT2 过表达和敲低的稳定转染的 A549 和 H1299 细胞系。进行集落形成、划痕愈合、Transwell 和 CCK-8 测定，以分别评估 circMBOAT2 在存在或不存在去甲肾上腺素 (NE) 治疗的情况下对 NSCLC 细胞的增殖、迁移和侵袭的影响。此外，通过异位移植LLC和注射针对circMBOAT2的反义寡核苷酸（ASO）建立了慢性不可预测的轻度应激（CUMS）诱导的抑郁症小鼠模型，以评估慢性应激通过circMBOAT2对肿瘤发生的影响。此外，我们通过体内和体外沉默 CTCF，研究了 CCCTC 结合因子 (CTCF) 对 circMBOAT2 表达的调节作用。我们的结果显示 circMBOAT2 在 NSCLC 细胞系和肿瘤组织中显着上调。 circMBOAT2敲低抑制NSCLC细胞的增殖、迁移和侵袭，而NE治疗逆转了circMBOAT2敲低引起的细胞抑制作用。值得注意的是，CUMS 促进肿瘤生长，而沉默 circMBOAT2 则抑制体内肿瘤生长。此外，我们确定 CTCF 是 circMBOAT2 的上游调节因子，其在 NSCLC 细胞和组织中表现出上调。 CTCF 的敲低逆转了 CUMS 对 circMBOAT2 表达和肿瘤生长的促进作用。我们的研究结果证明 CTCF 通过 circMBOAT2 介导慢性应激，促进 NSCLC 进展。 circMBOAT2 可能作为 NSCLC 的潜在生物标志物和治疗靶点，以及治疗 NSCLC 患者的共病抑郁症。© 2024。作者。

Circular RNA (circRNA) has been demonstrated to play a pivotal role in tumor development. This study aimed to investigate the regulatory mechanism of circMBOAT2 in non-small cell lung cancer (NSCLC) and its association with tumor growth induced by chronic stress. We constructed stably transfected A549 and H1299 cell lines with circMBOAT2 overexpression and knockdown. Colony formation, scratch healing, Transwell and CCK-8 assays were conducted to evaluate the effects of circMBOAT2 in the presence or absence of norepinephrine (NE) treatment on the proliferation, migration, and invasion of NSCLC cells, respectively. Additionally, A chronic unpredictable mild stress (CUMS)-induced depression with heterotopic transplantation LLC and injection of antisense oligonucleotides (ASOs) targeting circMBOAT2 mouse model was established to evaluate the effect of chronic stress on tumorigenesis via circMBOAT2. Moreover, we investigated the regulatory effect of CCCTC binding factor (CTCF) on circMBOAT2 expression through in vivo and in vitro silencing of CTCF. Our results revealed a significant upregulation of circMBOAT2 in NSCLC cell lines and tumor tissues. circMBOAT2 knockdown inhibited the proliferation, migration, and invasion of NSCLC cells, while NE treatment reversed the cell suppression effect caused by circMBOAT2 knockdown. Notably, CUMS promoted tumor growth, while silencing circMBOAT2 inhibited tumor growth in vivo. Furthermore, we identified CTCF as the upstream regulator of circMBOAT2, which exhibited upregulation in NSCLC cells and tissues. Knockdown of CTCF reversed the promotional effect of CUMS on circMBOAT2 expression and tumor growth. Our findings provide evidence that CTCF mediates chronic stress in promoting of NSCLC progression through circMBOAT2. circMBOAT2 may serve as a potential biomarker and therapeutic target for NSCLC as well as the treatment of comorbid depression in NSCLC patients.© 2024. The Author(s).