K Jiang1, L-F Xie, T-Z Xiao, M-Y Qiu, W-L Wang. 1. General Surgery, Wuxi No. 4 People's Hospital, Affiliated Hospital of Jiangnan University, Wuxi, China. drraphaeljk@126.com.
Abstract
OBJECTIVE: Gastric cancer is the second highest mortality tumor and the fourth most common cancer worldwide that has high aggressiveness. MicroRNA-181d (miR-181d) has been established to be a tumor suppressor, by suppressing cell proliferation, cell cycle, and promoting apoptosis in several cancers. The purpose of this study is to explore the great roles of miR-181d in gastric cancer. PATIENTS AND METHODS: The Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were applied to calculate the mRNA and protein levels of miR-181d and genes. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays were utilized to measure the proliferative and invasive abilities. The Kaplan-Meier method was conducted to calculate the overall survival of gastric cancer patients. RESULTS: MiR-181d was detected to be downregulated in gastric cancer tissues and cell lines compared to the peritumoral normal tissues and normal cell line. Downregulation of miR-181d predicted poor prognosis of gastric cancer patients. Cylindromatosis gene (CYLD) was overexpressed in gastric cancer tissues, which was confirmed to be a target gene of miR-181d in gastric cancer cell line HGC-27. Moreover, miR-181d inhibited the proliferation through CYLD/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway and inhibited the invasion-mediated epithelial-mesenchymal transition (EMT) in HGC-27 cells. In addition, overexpression of miR-181d suppressed tumor growth and xenograft tumorigenesis of HGC-27 cells in vivo. CONCLUSIONS: MiR-181d functioned as a tumor suppressor by inhibiting the proliferation via PI3K/AKT pathway in vitro and in vivo and inhibiting invasion-mediated epithelial-mesenchymal transition (EMT) by targeting CYLD in gastric cancer. The newly identified miR-181d/CYLD axis provides novel insight into the pathogenesis of gastric cancer.
OBJECTIVE:Gastric cancer is the second highest mortality tumor and the fourth most common cancer worldwide that has high aggressiveness. MicroRNA-181d (miR-181d) has been established to be a tumor suppressor, by suppressing cell proliferation, cell cycle, and promoting apoptosis in several cancers. The purpose of this study is to explore the great roles of miR-181d in gastric cancer. PATIENTS AND METHODS: The Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were applied to calculate the mRNA and protein levels of miR-181d and genes. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays were utilized to measure the proliferative and invasive abilities. The Kaplan-Meier method was conducted to calculate the overall survival of gastric cancerpatients. RESULTS:MiR-181d was detected to be downregulated in gastric cancer tissues and cell lines compared to the peritumoral normal tissues and normal cell line. Downregulation of miR-181d predicted poor prognosis of gastric cancerpatients. Cylindromatosis gene (CYLD) was overexpressed in gastric cancer tissues, which was confirmed to be a target gene of miR-181d in gastric cancer cell line HGC-27. Moreover, miR-181d inhibited the proliferation through CYLD/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway and inhibited the invasion-mediated epithelial-mesenchymal transition (EMT) in HGC-27 cells. In addition, overexpression of miR-181d suppressed tumor growth and xenograft tumorigenesis of HGC-27 cells in vivo. CONCLUSIONS:MiR-181d functioned as a tumor suppressor by inhibiting the proliferation via PI3K/AKT pathway in vitro and in vivo and inhibiting invasion-mediated epithelial-mesenchymal transition (EMT) by targeting CYLD in gastric cancer. The newly identified miR-181d/CYLD axis provides novel insight into the pathogenesis of gastric cancer.
Authors: Nikhil T Sebastian; Amy Webb; Kenneth W Merrell; Eugene J Koay; Adam R Wolfe; Lizhi Zhang; Tyler J Wilhite; Dalia Elganainy; Ryan Robb; Wei Chen; Jordan Cloyd; Mary Dillhoff; Allan Tsung; Laith Abushahin; Anne Noonan; Terence M Williams Journal: Cancers (Basel) Date: 2021-10-15 Impact factor: 6.575