Jie Zhou: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Peiwei Li: Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Xiaogang Zhao: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yuanhao Zhao: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Junwen Luo: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yupeng Deng: Department of Pathology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Ning Jiang: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Zhaohua Xiao: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Wenhao Zhang: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yongjia Zhou: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Jiangfeng Zhao: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Peichao Li: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yuliang Li: Department of Interventional Medicine, The Second Hospital, Cheello College of Medicine, Shandong University, Jinan, Shandong, China. lyl.pro@sdu.edu.cn.
Zhongxian Tian: Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. tianzhongxian@email.sdu.edu.cn.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
