 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 09, 2021 |
| Title |
MiR-484 Knockdown Ameliorates Liver Fibrosis by Blocking Wnt/β-catenin Pathway via Tar-geting HIPK1 |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Liver fibrosis is a common pathological process of various chronic liver diseases that can develop into liver cancer. MicroRNAs (miRNAs) are a king of non-coding RNA which are closely related to liver diseases. Thus, this research hope to explore the effect of miR-484 on liver fibrosis and reveal its mechanism. The miRNAs profiles were screened by microRNA sequencing and the location of miR-484 was identified by fluorescence in situ hybridization (FISH) in human liver fibrotic tissues. MiR-484 expression was detected by qRT-PCR in rat primary hepatic stellate cells (HSCs). Bioinformatics analysis and dual-luciferase reporter assay were performed to determine the target gene of miR-484. Liver fibrosis specific signatures were analyzed by qRT-PCR and western blot after miR-484 mimic/inhibitor transfection. The cell apoptosis was detected by Annexin V-FITC/PI double staining. The effect of miR-484 silencing on fibrosis in vivo was investigated in thioacetamide (TAA) induced mice model using the adeno-associated virus carrying miR-484 inhibitor. Enrichment of miR-484 was observed in human liver fibrosis tissues and activated rat primary HSCs. FISH showed that miR-484 was prominently located at fibrotic region and the cytoplasm of HSCs in human liver tissues. Dual-luciferase reporter assay verified that the homeodomain-interacting protein kinases 1 (HIPK1) was the direct target of miR-484. After transfecting miR-484 inhibitor into HSC-T6, HIPK1 were significantly up-regulated, and α-SMA, col1a1, Wnt-3a, Wnt-5a, β-catenin and p-β-catenin were down-regulated, suggesting the restrain effect of miR-484 knockdown on HSCs activation. Conversely, the results were opposite with miR-484 mimic transfection. In addition, the apoptosis of HSC-T6 altered significantly after miR-484 modulation. Moreover, adeno-associated virus carrying miR-484 inhibitor alleviated mice liver fibrosis induced by TAA. In conclusion, miR-484 knockdown ameliorates liver fibrosis by promoting the apoptosis and suppressing HSCs activation via blocking Wnt/β-catenin signaling pathway. MiR-484 and its downstream gene HIPK1 might be selected as novel therapeutic targets of liver fibrosis.
|
| |
|
| Overall design |
six human liver fibrotic tissues (provided by the Second Affiliated Hospital of Naval Medical Universi-ty, Shanghai, China) were gathered and sent for miRNA sequencing (Lc-bio technologies, Hangzhou, China).
|
| |
|
| Contributor(s) |
LI B, LUO Y, TAO K, ZHANG L, YU H, LIN Y, ZENG X |
| Citation(s) |
36467040 |
| |
| Submission date |
Dec 07, 2021 |
| Last update date |
Jan 03, 2023 |
| Contact name |
Xie qin |
| E-mail(s) |
qxie@lc-bio.com
|
| Phone |
15618926050
|
| Organization name |
LC sciences
|
| Street address |
Minchi first road, pujiang town, minhang district, Shanghai
|
| City |
shanghai |
| ZIP/Postal code |
200000 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA786876 |
| SRA |
SRP349641 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE190366_Processeddata.xlsx |
140.3 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...