OncoTargets and Therapy (Oct 2020)
Exosomal miR-548c-5p Regulates Colorectal Cancer Cell Growth and Invasion Through HIF1A/CDC42 Axis
Abstract
Shushan Yan,1 Xiaoxia Ren,2 Jinghan Yang,3 Jinghua Wang,3 Quan Zhang,4 Donghua Xu3 1Department of Gastrointestinal and Anal Diseases Surgery of Affiliated Hospital, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, Yantai Shan Hospital, Yantai, Shandong Province, People’s Republic of China; 3Central Laboratory and Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 4Department of Cardiology of Affiliated Hospital, Weifang Medical University, Weifang, Shandong Province, People’s Republic of ChinaCorrespondence: Donghua XuCentral Laboratory and Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, People’s Republic of ChinaEmail [email protected] ZhangDepartment of Cardiology of Affiliated Hospital, Weifang Medical University, Weifang, Shandong Province, People’s Republic of ChinaEmail [email protected]: Mounting evidence has implicated that exosomes-delivered noncoding RNAs are key regulators in carcinogenesis. The effect of miR-548c-5p has been elucidated in some cancers. However, the role of exosomal miR-548c-5p in colorectal cancer (CRC) is not fully understood. We aim to explore the function and mechanism of exosome-delivered miR-548c-5p in CRC. The altering effect of exosome-derived miR-548c-5p on the prognosis of CRC patients is also investigated by estimating overall survival and disease-free survival.Materials and Methods: The expression of miR-548c-5p in exosomes is determined by real-time PCR. The proliferation and invasion of CRC cells are estimated by MTT, transwell assay and scratch test. The targeted gene of miR-548c-5p is investigated by luciferase reporter assay, real-time PCR, Western blot and chromosome immunoprecipitation (CHIP) assay. CRC cells are transplanted subcutaneously in BALB/c nude mice to estimate their growth in vivo.Results: MiR-548c-5p derived from CRC cell exosomes inhibits the proliferation and invasion of CRC cells in vitro. Exosomal miR-548c-5p can also prevent from colorectal carcinogenesis in nude mice in vivo. HIF1A is documented to be a target of miR-548c-5p, and HIF1A can targetedly regulate CDC42 in CRC cells. Exosomal miR-548c-5p affects CRC cell growth, migration and invasion via miR-548c-5p/HIF1A/CDC42 axis. In addition, exosomal miR-548c-5p can be a predictive factor for CRC prognosis.Conclusion: Our study has suggested that exosomal miR-548c-5p can regulate CRC through HIF1A/CDC42 axis, which helps to understand CRC pathogenesis more clearly and identify novel therapeutic strategies for CRC patients.Keywords: CDC42, colorectal cancer, exosome, HIF1A, microRNA
