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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Li, Wenjing Li, Jun Mu, Hong Guo, Meiqi Deng, Haixia |
| Abstract | Background Abnormal expression of microRNAs (miRNAs) is related to human carcinogenesis. Although previous studies have shown that miR-503 expression in gastric cancer (GC) is downregulated, however, the underlying molecular mechanism for miR-503 involved in gastric cancer development is still largely unknown. Methods The relative expression of miR-503 in GC tissues and adjacent normal tissues was examined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses. In vitro, cell proliferation and invasion were evaluated by using CCK8, cell colony and transwell invasion assays. In vivo, xenograft tumor model was constructed to assess miR-503 expression whether affects tumor growth or not. Luciferase reporter assay, qRT-PCR and western blot assay were used to demonstrate HMGA2 is a target of miR-503. Results We demonstrated that miR-503 expression was significantly downregulated in GC tissues and cell lines compared to adjacent normal tissues and normal gastric mucosa cell lines, respectively. Lower miR-503 expression associated with tumor size, lymph node metastasis, and predicted a poor overall survival (OS) time in GC patients. Subsequently, in vitro, gain-function and loss-function assays confirmed that miR-503 overexpression significantly suppressed GC cell proliferation, colony formation and cell invasion, while decreased miR-503 expression had an adverse effect in GC cells. Furthermore, we found that miR-503 specifically targeted the 3′-UTR regions of HMGA2 mRNA and suppressed its protein expression. Overexpression of HMGA2 could reverse the miR-503 mediated inhibition of GC cell proliferation and invasion. In vivo, miR-503 overexpression dramatically reduced tumor growth. Moreover, we demonstrated that miR-503 suppressed WNT/β-catenin signaling by elevating GSK-3β and p-β-catenin expression, but decreased p-GSK-3β and β-catenin expression in GC cells. Conclusion These results provide that miR-503 expression acts as a predictor for GC prognosis and may have a potential application in GC therapy. |
| Related Links | https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-019-0875-1.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752867 |
| DOI | 10.1186/s12935-019-0875-1 |
| Journal | Cancer Cell International |
| Issue Number | 1 |
| Volume Number | 19 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2019-06-14 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Cell Biology Gastric cancer miR-503 HMGA2 Cell proliferation Cell invasion |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Genetics Oncology |
| Journal Impact Factor | 5.3/2023 |
| 5-Year Journal Impact Factor | 5/2023 |
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