title: miR-489 acts as a tumor suppressor in human gastric cancer by targeting PROX1.
abstract: Dysregulation of microRNAs (miRNAs) are linked to tumorigenesis and tumor progression. In this study, we examined the expression of miR-489 in gastric cancer tissues and cells. Loss- and gain-of-function experiments were done to determine the roles of miR-489 in gastric cancer cell proliferation and invasion. Bioinformatic prediction, luciferase reporter assays, and Western blot analysis were employed to identify the target gene(s) of miR-489. We found that miR-489 was significantly (P< 0.05) downregulated in human gastric cancer tissues and cell lines, compared to their non-malignant counterparts. Enforced expression of miR-489 significantly suppressed gastric cancer cell proliferation and invasion, while miR-489 knockdown enhanced the aggressive behaviors of gastric cancer cells. Prospero homeobox 1 (PROX1) was identified to be a direct target of miR-489. A significant negative correlation was seen between miR-489 and PROX1 protein expression in gastric cancer tissues (r= -0.462,P= 0.023). Silencing of PROX1 phenocopied the suppressive effects of miR-489 in gastric cancer cells. Rescue experiments demonstrated that overexpression of a miR-489-resistant form of PROX1 significantly prevented the reduction in cell proliferation and invasion induced by miR-489 overexpression. In vivo studies confirmed that miR-489 overexpression retarded the growth of xenograft tumors, which was accompanied by reduced PROX1 expression. Overall, these data provide evidence for the suppressive activity of miR-489 in gastric cancer, which is ascribed to targeting of PROX1. The miR-489/PROX1 axis may represent a potential therapeutic target for this disease.
authors.affiliation: Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, China.
authors.forename: Sheqing
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
keywords: Gastric cancer; invasiveness; microRNA; target genes; tumorigenesis