ArticleOncogene2018
SRGAP1, a crucial target of miR-340 and miR-124, functions as a potential oncogene in gastric tumorigenesis.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 67 citations in OpenAlex.
- Review
- MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1.International journal of molecular sciences · 2023Article
- LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis.International journal of molecular sciences · 2023Article
- Regulation of the Key Epithelial Cancer Suppressor miR-124 Function by Competing Endogenous RNAs.International journal of molecular sciences · 2022Review
- A proliferative to invasive switch is mediated by srGAP1 downregulation through the activation of TGF-β2 signaling.Cell reports · 2022Article
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- LncRNA SND1-IT1 facilitates TGF-β1-induced epithelial-to-mesenchymal transition via miR-124/COL4A1 axis in gastric cancer.Cell death discovery · 2022Article
- The emerging roles of srGAPs in cancer.Molecular biology reports · 2022Review
- Overexpression of miR-340 inhibits cell proliferation and induces apoptosis of human bladder cancer via targeting Glut-1.BMC urology · 2021Article
- miR-340: A multifunctional role in human malignant diseases.International journal of biological sciences · 2021Review
- Restoration of miR-340 controls pancreatic cancer cellJournal for immunotherapy of cancer · 2020Article
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340.Molecular cancer · 2020Article
- Differentially methylated gene patterns between age-matched sarcopenic and non-sarcopenic women.Journal of cachexia, sarcopenia and muscle · 2019Article
- MicroRNA-124: An emerging therapeutic target in cancer.Cancer medicine · 2019Review
- Effects of miR‑340 overexpression and knockdown on the proliferation and metastasis of NSCLC cell lines.International journal of molecular medicine · 2019Article
- miR-340-FHL2 axis inhibits cell growth and metastasis in ovarian cancer.Cell death & disease · 2019Article
- Mechanotransduction and Cytoskeleton Remodeling Shaping YAP1 in Gastric Tumorigenesis.International journal of molecular sciences · 2019Review
- Expression of miR-124 in gastric adenocarcinoma and the effect on proliferation and invasion of gastric adenocarcinoma SCG-7901 cells.Oncology letters · 2019Article
- Article
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Slit-Robo GTPase-activating protein 1 (SRGAP1) functions as a GAP for Rho-family GTPases and downstream of Slit-Robo signaling. We aim to investigate the biological function of SRGAP1 and reveal its regulation by deregulated microRNAs (miRNAs) in gastric cancer (GC). mRNA and protein expression of SRGAP1 were examined by quantitative reverse transcription PCR (qRT-PCR) and western blot. The biological role of SRGAP1 was demonstrated through siRNA-mediated knockdown experiments. The regulation of SRGAP1 by miR-340 and miR-124 was confirmed by western blot, dual luciferase activity assays and rescue experiments. SRGAP1 is overexpressed in 9 out of 12 (75.0%) GC cell lines. In primary GC samples from TCGA cohort, SRGAP1 shows gene amplification in 5/258 (1.9%) of cases and its mRNA expression demonstrates a positive correlation with copy number gain. Knockdown of SRGAP1 in GC cells suppressed cell proliferation, reduced colony formation, and significantly inhibited cell invasion and migration. Luciferase reporter assays revealed that SRGAP1 knockdown significantly inhibited Wnt/β-catenin pathway. In addition, SRGAP1 was found to be a direct target of two tumor-suppressive miRNAs, miR-340 and miR-124. Concordantly, these two miRNAs were downregulated in primary gastric tumors and these decreasing levels w5ere associated with poor outcomes. Expression of miR-340 and SRGAP1 displayed a reverse relationship in primary samples and re-expressed SRGAP1, rescued the anti-cancer effects of miR-340. Taken together, these data strongly suggest that, apart from gene amplification and mutation, the activation of SRGAP1 in GC is partly due to the downregulation of tumor-suppressive miRNAs, miR-340 and miR-124. Thus SRGAP1 is overexpressed in gastric carcinogenesis and plays an oncogenic role through activating Wnt/β-catenin pathway.
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