OncoTargets and Therapy (Jan 2020)
Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a
Abstract
Yong Liu,1,* Chuanping Yang,2,* Chengsong Cao,1 Qing Li,1 Xin Jin,1 Hanping Shi3– 5 1Department of Oncology, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine, Nanjing Medical University, Xuzhou 221000, People’s Republic of China; 2Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine, Nanjing Medical University, Xuzhou 221000, People’s Republic of China; 3Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 4Department of Oncology, Capital Medical University, Beijing 100069, People’s Republic of China; 5Beijing International Science and Technology Cooperation Base of Tumor Metabolism and Nutrition, Beijing 100038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hanping Shi Fax +86-0951-6743244Email [email protected]: Circular RNA (circRNA) is involved in the development of various cancers. However, whether circRNA can inhibit the tumorigenesis of non-small cell lung cancer (NSCLC) is still unclear. We aimed to explore the epigenetic function of tumor-suppressive circRNA (hsa_circ_RNA_0011780) and its downstream regulatory factors in NSCLC.Patients and Methods: Quantitative polymerase chain reaction (qPCR) was used to evaluate hsa_circ_11780 expression in NSCLC tissues and cell lines. The impact of high hsa_circ_11780 expression on overall survival in patients with NSCLC was tested using the Log rank test. The association between decreased hsa_circ_11780 expression and clinicopathological features in patients with NSCLC was analyzed using the Chi-squared test. In vitro cell proliferation and apoptosis were assayed using the cell counting kit-8 (CCK-8) and flow cytometry, respectively. Mice xenograft models were used to determine the tumor promoting effects of hsa_circ_11780 on NSCLC in vivo. The underlying regulatory mechanism was predicted by bioinformatics and verified by a dual-luciferase reporter assay, RNA transfection, qPCR, and Western blotting. The correlation between miR-544a and hsa_circ_11780 expression was verified using Spearman correlation coefficient.Results: The expression of hsa_circ_11780 in NSCLC tissues and cell lines strongly declined. Low hsa_circ_11780 expression is more likely to present in patients with a large tumor size (> 3cm), distant metastasis, and poor overall survival. hsa_circ_11780 overexpression strongly inhibited proliferation, migration, and invasion of NSCLC cells (H226 and A549) in vitro and inhibited tumor growth in vivo. Furthermore, hsa_circ_11780 repressed miR-544a function by competitively binding to the complementary sites of miR-544a. miR-544a released by the declining expression of hsa_circ_11780 reduced the protein concentration of F-Box and WD repeat domain containing 7 (FBXW7) in NSCLC cells.Conclusion: FBXW7 expression mediated by the hsa_circ_11780/miR-544a axis is markedly associated with the proliferation, migration, and invasion of NSCLC, resulting in decreased survival. These findings suggest that this regulatory axis may serve as a novel therapeutic target in NSCLC.Keywords: non-small cell lung cancer, hsa_circ_11780, F-box and WD repeat domain containing 7, miR-544a, proliferation, metastasis
