环状 RNA hsa_circ_0004689（circSWT1）通过诱导细胞上皮-间充质转化（EMT），经由 miR-370-3p/SNAIL 轴促进 NSCLC 的进展。
Circular RNA hsa_circ_0004689 (circSWT1) promotes NSCLC progression via the miR-370-3p/SNAIL axis by inducing cell epithelial-mesenchymal transition (EMT).
机构信息
Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
出版信息
Cancer Med. 2023 Apr;12(7):8289-8305. doi: 10.1002/cam4.5527. Epub 2022 Dec 19.
BACKGROUND
Previous studies have reported the role of circular RNAs (circRNAs) in the progression of non-small-cell lung cancer (NSCLC). SWT1-derived circRNAs were confirmed to affect the apoptosis of cardiomyocytes; however, the biological functions of SWT1-derived circRNAs in cancers are still unknown. Here, we investigated the potential role of SWT1-derived circRNAs in NSCLC.
METHODS
We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression of circSWT1 in NSCLC tissues and paired normal tissues. The potential functions of circSWT1 in tumor progression were assessed by CCK-8, colony formation, wound healing, and matrigel transwell assays in vitro and by xenograft tumor models in vivo. Next, epithelial-mesenchymal transition (EMT) was evaluated by western blotting, immunofluorescence, and immunohistochemistry (IHC). Moreover, circRIP, RNA pulldown assays, luciferase reporter gene assays, and FISH were conducted to illuminate the molecular mechanisms of circSWT1 via the miR-370-3p/SNAIL signal pathway. Then, we knocked out SNAIL in A549 and H1299 cells to identify the roles of circSWT1 in the progression and EMT of NSCLC through SNAIL. Finally, circSWT1 functions were confirmed in vivo using xenograft tumor models.
RESULTS
CircSWT1 expression was significantly upregulated in NSCLC tissues, and high expression of circSWT1 predicted poor prognosis in NSCLC via survival analysis. In addition, overexpression of circSWT1 promoted the invasion and migration of NSCLC cells. Subsequently, we found that overexpression of circSWT1 induced EMT and that knockdown of circSWT1 inhibited EMT in NSCLC cells. Mechanistically, circSWT1 relieved the inhibition of downstream SNAIL by sponging miR-370-3p. Moreover, we found that these effects could be reversed by knocking out SNAIL. Finally, we verified that circSWT1 promoted NSCLC progression and EMT in xenograft tumor models.
CONCLUSION
CircSWT1 promoted the invasion, migration, and EMT of NSCLC. CircSWT1 could serve as a potential biomarker and a potential therapeutic target for NSCLC.
背景
先前的研究报告表明环状 RNA（circRNA）在非小细胞肺癌（NSCLC）的进展中发挥作用。SWT1 衍生的 circRNAs 被证实影响心肌细胞的凋亡；然而，SWT1 衍生的 circRNAs 在癌症中的生物学功能仍然未知。在这里，我们研究了 SWT1 衍生的 circRNAs 在 NSCLC 中的潜在作用。
方法
我们使用实时定量聚合酶链反应（qRT-PCR）测量 NSCLC 组织和配对正常组织中 circSWT1 的表达。通过体外 CCK-8、集落形成、划痕愈合和基质胶 Transwell 测定以及体内异种移植肿瘤模型评估 circSWT1 在肿瘤进展中的潜在功能。接下来，通过 Western blot、免疫荧光和免疫组织化学（IHC）评估上皮-间充质转化（EMT）。此外，通过 circRIP、RNA 下拉测定、荧光素酶报告基因测定和 FISH 进行研究，以阐明 circSWT1 通过 miR-370-3p/SNAIL 信号通路的分子机制。然后，我们在 A549 和 H1299 细胞中敲除 SNAIL，以通过 SNAIL 鉴定 circSWT1 在 NSCLC 进展和 EMT 中的作用。最后，通过异种移植肿瘤模型在体内验证 circSWT1 的功能。
结果
circSWT1 在 NSCLC 组织中表达明显上调，通过生存分析发现 circSWT1 高表达预示 NSCLC 预后不良。此外，circSWT1 的过表达促进了 NSCLC 细胞的侵袭和迁移。随后，我们发现过表达 circSWT1 诱导 EMT，而在 NSCLC 细胞中敲低 circSWT1 抑制 EMT。机制上，circSWT1 通过海绵吸附 miR-370-3p 减轻下游 SNAIL 的抑制作用。此外，我们发现这些作用可以通过敲除 SNAIL 逆转。最后，我们验证了 circSWT1 在异种移植肿瘤模型中促进 NSCLC 进展和 EMT。
结论
circSWT1 促进 NSCLC 的侵袭、迁移和 EMT。circSWT1 可以作为 NSCLC 的潜在生物标志物和潜在治疗靶点。
Zotero 插件