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miR-489 acts as a tumor suppressor in human gastric cancer by targeting PROX1.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Zhang, Bin Ji, Sheqing Lu, Xianzhi Chen, Xiaobing |
| Copyright Year | 2016 |
| 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. |
| Starting Page | 2021 |
| Ending Page | 2030 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 27725907 |
| Journal | Medline |
| Volume Number | 6 |
| Issue Number | 9 |
| Alternate Webpage(s) | http://www.ajcr.us/files/ajcr0036247.pdf |
| Journal | American journal of cancer research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
