| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 406976 |
Name | MIR199A1 |
Synonymous | microRNA 199a-1;MIR199A1;microRNA 199a-1 |
Definition | hsa-mir-199a-1 |
Position | 19p13.2 |
Gene type | ncRNA |
Title | Abstract |
| Functional screening for miRNAs targeting Smad4 identified miR-199a as a negative regulator of TGF-beta signalling pathway. | The transforming growth factor-beta (TGF-beta) signalling pathway participates in various biological processes. Dysregulation of Smad4, a central cellular transducer of TGF-beta signalling, is implicated in a wide range of human diseases and developmental disorders. However, the mechanisms underlying Smad4 dysregulation are not fully understood. Using a functional screening approach based on luciferase reporter assays, we identified 39 microRNAs (miRNAs) as potential regulators of Smad4 from an expression library of 388 human miRNAs. The screening was supported by bioinformatic analysis, as 24 of 39 identified miRNAs were also predicted to target Smad4. MiR-199a, one of the identified miRNAs, was inversely correlated with Smad4 expression in various human cancer cell lines and gastric cancer tissues, and repressed Smad4 expression and blocked canonical TGF-beta transcriptional responses in cell lines. These effects were dependent on the presence of a conserved, but not perfect seed paired, miR-199a-binding site in the Smad4 3 -untranslated region (UTR). Overexpression of miR-199a significantly inhibited the ability of TGF-beta to induce gastric cancer cell growth arrest and apoptosis in vitro, and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis. In conclusion, our functional screening uncovers multiple miRNAs that regulate the cellular responsiveness to TGF-beta signalling and reveals important roles of miR-199a in gastric cancer by directly targeting Smad4. |
| Up-regulated miR-199a-5p in gastric cancer functions as an oncogene and targets klotho. | BACKGROUND: Recent studies have shown that miR-199a-5p plays opposite roles in cancer initiation and progression of different cancer types, acting as oncogene for some cancer types but as tumor suppressor gene for others. However, the role and molecular mechanism of miR-199a-5p in gastric cancer are largely unknown. METHODS: In this study, miR-199a-5p expression level in gastric cancer was first analyzed by qPCRand then validated in 103 gastric cancer patients by in situ hybridization (ISH). Gastric cancer cell lines were transfected with miR-199a-5p inhibitor and mimic, and underwent in vitro transwell assays. Target genes (klotho) were identified using Luciferase reporter assay. Immunohistochemical staining was also used to investigate on how miR-199a-5p regulates the tumour-suppressive effects of klotho in gastric cancer. RESULTS: In our present study, we found that miR-199a-5p level was significantly increased in gastric cancer tissues compared to paired normal tissues. We observed that miR-199a-5p could promote migration and invasion of gastric cancer cells. In situ hybridization of miR-199a-5p also confirmed that higher miR-199a-5p expression level was associated with increased likelihood of lymph node metastasis and later TNM stage. Luciferase reporter assay and immunohistochemistry revealed that klotho might be the downstream target of miR-199a-5p. CONCLUSIONS: Our present study suggests that miR-199a-5p acts as an oncogene in gastric cancer and functions by targeting klotho. |