研究动态
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Circ_16601 通过 miR-5580-5p/FGB 轴促进 Hippo 通路信号传导,从而促进 TME 和 LUAD 进展中 my-CAF 的募集。

Circ_16601 facilitates Hippo pathway signaling via the miR-5580-5p/FGB axis to promote my-CAF recruitment in the TME and LUAD progression.

发表日期:2023 Nov 12
作者: Jie Zhou, Peiwei Li, Xiaogang Zhao, Yuanhao Zhao, Junwen Luo, Yupeng Deng, Ning Jiang, Zhaohua Xiao, Wenhao Zhang, Yongjia Zhou, Jiangfeng Zhao, Peichao Li, Yuliang Li, Zhongxian Tian
来源: GENES & DEVELOPMENT

摘要:

鉴于其高发病率和死亡率,肺癌是中国的一个重大公共卫生问题。最近提出环状RNA(circRNA)参与肿瘤的发生和进展。然而,它们在肺腺癌(LUAD)发病机制、肿瘤微环境(TME)中的特殊作用以及潜在的分子机制仍不清楚。利用高通量测序分析了7对人类中的circRNA表达谱LUAD 组织。 shRNA 用于敲低 YAP1 和 FGB 基因。通过 RNA 测序和 RT-qPCR 对 circ_16601 在 LUAD 细胞中的调节作用进行分类。体外和体内研究了circ_16601对肺癌进展的影响。与邻近正常肺组织相比,circ_16601在LUAD组织中显着升高,其高表达与LUAD患者不良预后呈正相关。此外,circ_16601 过表达可促进 LUAD 细胞体外增殖,并增加小鼠体内异种移植组织的生长; circ_16601 还可以招募成纤维细胞成为癌症相关成纤维细胞。从机制上讲,circ_16601可以直接与miR-5580-5p结合,防止其降解FGB mRNA并增强其稳定性。随后,circ_16601 以 YAP1 依赖性方式促进 Hippo 通路的激活,导致 LUAD 进展。我们的研究结果为了解 circ_16601 在 LUAD 进展中的调节作用提供了宝贵的见解,并强调了其作为 LUAD 诊断和治疗靶点的潜力。总的来说,这项研究为改善这种毁灭性疾病患者的预后和生活质量提供了理论支持。© 2023。作者。
Lung cancer represents a significant public health issue in China, given its high incidence and mortality rates. Circular RNAs (circRNAs) have been recently proposed to participate in the development and progression of tumors. Nevertheless, their particular roles in the pathogenesis of lung adenocarcinoma (LUAD), the tumor microenvironment (TME), and the underlying molecular mechanisms are still not well understood.High-throughput sequencing was used to analyze the circRNAs expression profiles in 7 pairs of human LUAD tissues. shRNA was used to knockdown the YAP1 and FGB genes. RNA sequencing and RT-qPCR were performed to classify the regulatory effects of circ_16601 in LUAD cells. The progression effect of circ_16601 on lung cancer was investigated in vitro and in vivo.The circ_16601 is significantly elevated in LUAD tissues compared to adjacent normal lung tissues, and its high expression is positively associated with poor prognosis in LUAD patients. Additionally, circ_16601 overexpression promotes LUAD cell proliferation in vitro and increases xenograft tissue growth in mice in vivo; circ_16601 also could recruit fibroblasts to cancer associate fibroblasts. Mechanistically, circ_16601 can directly bind to miR-5580-5p, preventing its ability to degrade FGB mRNA and enhancing its stability. Subsequently, circ_16601 promotes the activation of the Hippo pathway in a YAP1-dependent manner, leading to LUAD progression.Our findings shed valuable insights into the regulatory role of circ_16601 in LUAD progression and highlight its potential as a diagnostic and therapeutic target in LUAD. Overall, this study provides theoretical support to improve the prognosis and quality of life of patients suffering from this devastating disease.© 2023. The Author(s).