| Gene name: | MIR34A |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | HepG2,SMMC-7721,HHCC,SK-Hep-1 |
| Gene ID: | 407040 |
| Category: | ncRNA |
| Phenotype: | Hepatocellular carcinoma |
| Experimental category: | L |
| PMID: | 25686834 |
| Experiment: | SA-β-gal activity assay//Cell morphological analysis |
| Description: | We observed that introduction of miR-34a into liver cancer cells caused senescence-like phenotypes, with positive staining for senescence-associated β-galactosidase (SA β-gal) and enlarged cellular size. |
| Target gene: | C-MYC//FOXM1//P53 |
| Official symbol(s): | C-MYC//FOXM1//P53 |
| R-AG-Target gene: | Upregulation//Upregulation//-- |
| Subcategory: | Unclear |
| Target gene experiment: | qRT-PCR//Western blot//Luciferase reporter assay |
| Target gene description: | The data showed that among the hTERT activators examined, FoxM1 and c-Myc were the most down-regulated genes by miR-34a overexpression.By target prediction, it turned out that FoxM1 and c-Myc have predicted binding sites for miR-34a in their 3 UTRs. With the transfection of miR-34a duplex (miR-34a) in cancer cell lines, we found that miR-34a reduced the protein levels of c-Myc and FoxM1 significantly.Our results showed that miR-34a inhibited luciferase activity significantly, whereas no effect was observed when their respective target sites were mutated, suggesting that miR-34a directly targets c-Myc and FoxM1 via binding to the 3UTRs in liver cancer cells.The miR-34a expression positively correlated with the p53 level (P < 0.05), which was consistent with the NCI-60 data.Our expectation, the p53 protein expression significantly increased after treatment with H2 O2 or cisplatin in the wildtype p53 cells and the levels of miR-34a also increased accordingly.Further, when endogenous p53 expression was knocked down by a p53 siRNA in the four p53 wild-type liver cancer cells, miR-34a expression was also attenuated. |
| Regulatory pathway: | FOXM1-C-MYC |
| R-AG-Pathway: | -- |
| Official symbol(s): | FOXM1-MYC |
| Pathway experiment: | qRT-PCR//Western blot |
| Pathway description: | The effect of c-Myc overexpression rescued the FoxM1-mediated inhibition of hTERT, as revealed by qRT-PCR and western blot, suggesting c-Myc as one of the most important downstream factors of FoxM1. As altered expression of miR-34a would contribute to the impaired telomerase activity, we discovered similar effects of miR-34a mimics and FoxM1 siRNA on the hTERT expression, with possible synergistic effect when transfected together, as revealed by qRT-PCR and western blot. With no surprise, similar effects were also observed for miR34a mimics and c-Myc siRNA. |
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