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MicroRNA-188-5p targeting Forkhead Box L1 promotes colorectal cancer progression via activating Wnt/β-catenin signaling
Authors:JIALIN WU  ZEHONG CHEN  WENWEI LIU  YONGXIN ZHANG  WEI FENG  YUJIE YUAN  JINNING YE  LIANG WANG  SHIRONG CAI  YULONG HE  SUIJING WU  WU SONG
Institution:1 Center of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China2 Department of Hepatobiliary and Pancreatic Surgery, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, China3 Department of Gastrointestinal Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China4 Department of Hematology, Guangdong General Hospital, Guangzhou, China
Abstract:Objective: MicroRNA-188-5p (miR-188) enhances oncologic progression in various human malignancies. This study aimed to explore its role in colorectal cancer (CRC). Materials and Methods: Human CRC tissues paired with normal tissues, and several CRC cell lines were utilized. Real-time quantitative PCR was applied to measure the expression of miR-188. Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function. The proliferation, migration and invasion of cancer cells were evaluated by CCK8, wound-healing and transwell assays, respectively. Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays. Results: Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues, as well as in various CRC cell lines. High expression of miR-188 was strongly associated with advanced tumor stage, accompanied with significant tumor cell proliferation, invasion and migration. It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation. Conclusions: All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.
Keywords:miR-188  Colorectal adenocarcinoma  Oncogenesis  Oncologic progression  Wnt signaling
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