Excel · study · 2026
MicroRNA-34a Promotes Hepatic Lipid Accumulation through RXRα Suppression and Is Reversed by 9-cis-Retinoic Acid in Steatotic Hepatocytes
Listed in NCBI GEO
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide and is characterized by excessive hepatic lipid accumulation and metabolic dysregulation.
Description
Although microRNA-34a (miR-34a) has been implicated in lipid metabolism, the molecular mechanisms underlying its contribution to MAFLD remain incompletely understood. This study aimed to investigate the role of miR-34a in hepatic steatosis and to identify potential therapeutic targets.
An in vitro steatosis model was established using free fatty acid (FFA)-treated HepG2 cells. miR-34a expression was analyzed by RT-qPCR, and direct target interactions were validated using dual-luciferase reporter assays. Proteomic alterations were characterized by iTRAQ-based proteomic profiling, followed by Ingenuity Pathway Analysis (IPA). The therapeutic potential of retinoid X receptor alpha (RXRα) activation was evaluated using 9-cis-retinoic acid (9-cis-RA). miR-34a expression was significantly increased in FFA-treated hepatocytes and directly targeted the 3′-UTRs of PPARα, SIRT1, and RXRα.
Read the rest (2 more)
Integrated transcriptomic and proteomic analyses identified LXR/RXR signaling as a major pathway disrupted by miR-34a overexpression. RXRα was validated as a direct downstream target of miR-34a, establishing a mechanistic link between microRNA dysregulation and nuclear receptor signaling. Pharmacological activation of RXRα by 9-cis-RA markedly attenuated lipid accumulation and reduced the expression of key lipogenic and fatty acid uptake proteins, including FASN, SCD1, and CD36.
Our findings identify RXRα as a novel target of miR-34a and reveal a previously unrecognized miR-34a–RXRα regulatory axis governing hepatic lipid homeostasis. Activation of RXRα effectively reverses steatotic phenotypes, highlighting the miR-34a–RXRα axis as a potential therapeutic target for MAFLD.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337589 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337589 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1490448 ncbi.nlm.nih.gov/bioproject/PRJNA1490448 ↗
project · from NCBI GEO
- PubMed 42589269 pubmed.ncbi.nlm.nih.gov/42589269 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE337589 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |