Circular RNA sirtuin-1 restrains the malignant phenotype of non-small cell lung cancer cells via the microRNA-510-5p/SMAD family member 7 axis

ZiRan Zhao; HongYan Zhang; Fan Zhang; Ying Ji; Yue Peng; Fei Wang; Liang Zhao

doi:10.18388/abp.2020_6675

ZiRan Zhao Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, BeiJing, 100021, Chin
HongYan Zhang Department of Oncology, The Third Medical Center of PLA General Hospital, BeiJing, 100143, China
Fan Zhang Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, BeiJing, 100021, China
Ying Ji Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, BeiJing, 100021, China
Yue Peng Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, BeiJing, 100021, China
Fei Wang Department of Oncology, The Seventh Medical Center of PLA General Hospital, BeiJing, 100010, China
Liang Zhao Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, BeiJing, 100021, China https://orcid.org/0000-0002-7315-6853

DOI: https://doi.org/10.18388/abp.2020_6675

Abstract

Circular RNA (circRNA) sirtuin-1 (SIRT1) is differentially expressed in non-small cell lung cancer (NSCLC), but its specific mechanism is still uncertain. The study was to figure out the latent molecular mechanism of circSIRT1 in NSCLC. The results clarified that circSIRT1 and SMAD family member 7 (SMAD7) were downregulated, but microRNA (miR)-510-5p was upregulated in NSCLC. CircSIRT1 expression was linked with tumor–node–metastasis staging and tumor size in NSCLC patients. Elevating circSIRT1 or suppressing miR-510-5p refrained NSCLC cell activities and glycolysis and inactivated the wnt/β-catenin pathway, while knockdown of circSIRT1 promoted the malignant behavior of NSCLC cells. Besides, inhibition of malignant behavior in NSCLC cells by elevating circSIRT1 was reversed by knockdown of SMDA7. circSIRT1 bound to miR-510-5p to target SMAD7. In short, circSIRT1 represses NSCLC cell malignant development via miR-510-5p to target SMAD7, making it a latent target for NSCLC treatment.