title: 18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling.
abstract: 18β-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA. miR-149-3p expression also correlated negatively with lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression inhibited cell proliferation and cell cycle progression while inducing apoptosis, while inhibition of miR-149-3p had the opposite effects. In addition, we identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA inhibits the initiation and progression of gastric tumors by ameliorating the inflammatory microenvironment through downregulation of COX-2 expression and by inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149-3p. GRA may thus have the potential to serve as a useful therapeutic agent for the prevention and treatment of gastric cancer.
authors.affiliation: Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Cao
authors.affiliation: Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Lili
authors.initials: L
authors.lastname: You
authors.affiliation: Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Yueer
authors.initials: Y
authors.lastname: Suo
authors.affiliation: Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Houjun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Simin
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Diagnostic Pathology I, School of Medicine, Fujita Health University, Toyoake, 470-1192, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsukamoto
authors.affiliation: Cancer Research Institute, Kanazawa University, Kanazawa, 920-1192, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis; D005260:Female; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000473:pathology / Q000517:prevention & control*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051155:Wnt1 Protein / Q000235:genetics / Q000502:physiology*
chemical_list: C551557:MIRN149 microRNA, human; D035683:MicroRNAs; D051155:Wnt1 Protein; C119129:18alpha-glycyrrhetinic acid; D051546:Cyclooxygenase 2; D006034:Glycyrrhetinic Acid
keywords: 18β-glycyrrhetinic acid; COX-2; Wnt-1; gastric cancer; miR-149-3p