| 1994 |
The FDFT1 (squalene synthase) gene was mapped to human chromosome 8p22-p23.1 using fluorescence in situ hybridization (FISH) with a YAC containing the gene, confirmed by PCR of somatic cell hybrids. |
FISH, somatic cell hybrid PCR mapping |
Genomics |
High |
8020937
|
| 2007 |
The Fdft1 gene in rats harbors a hypomorphic allele (Fdft1(S)) with a missense nucleotide substitution that reduces cholesterol biosynthesis function; this allele is widely prevalent across laboratory rat strains and was identified as a determinant of hereditary cataracts in the SCR rat strain. |
Genetic screening, sequencing, functional characterization of mutant alleles |
Experimental animals |
Medium |
17460354
|
| 2020 |
FDFT1 acts as a tumor suppressor in colorectal cancer by negatively regulating AKT/mTOR/HIF1α signaling; fasting upregulates FDFT1 expression and inhibits aerobic glycolysis and proliferation in CRC cells through this pathway. |
Loss-of-function (siRNA knockdown), overexpression, in vitro proliferation/glycolysis assays, in vivo xenograft models, pathway inhibitor experiments |
Nature communications |
High |
32313017
|
| 2020 |
Bavachinin inhibits FDFT1 expression via the AKT/mTOR/SREBP-2 pathway in HepaRG cells; overexpression of FDFT1 abolished bavachinin-induced inhibition of cholesterol synthesis, establishing FDFT1 as a downstream effector of this pathway in cholesterol regulation. |
Overexpression rescue experiments, Western blot, lipid accumulation assays, pathway inhibitor analysis |
International immunopharmacology |
Medium |
32827918
|
| 2020 |
miR-4425 directly targets FDFT1 mRNA to suppress its expression; forced FDFT1 expression negates the tumorigenic properties of miR-4425 in ovarian cancer cells, establishing FDFT1 as a functional target of miR-4425. |
Luciferase reporter assay, Western blot, siRNA knockdown, overexpression rescue, in vivo xenograft |
Archives of biochemistry and biophysics |
High |
32877662
|
| 2024 |
Somatic bi-allelic genetic and/or epigenetic (promoter hypermethylation) silencing of FDFT1 causes clonal expansion of FDFT1-deficient keratinocytes, resulting in porokeratosis; FDFT1-deficient keratinocytes showed cholesterol dependence for cell growth and altered cell-cycle and epidermal development gene expression. Topical statin treatment ameliorated lesions, confirming FDFT1's role in cholesterol synthesis in skin. |
Genomic sequencing, bisulfite sequencing (methylation analysis), IHC for FDFT1 localization in lesions, keratinocyte culture with cholesterol rescue, RT-PCR for gene expression |
American journal of human genetics |
High |
38653249
|
| 2024 |
Artemisitene (ATT) directly binds FDFT1 in breast cancer cells, as confirmed by CETSA, SPR, and molecular docking. Knockdown of FDFT1 induced NEDD4 expression and apoptosis via the TNFR1/NF-κB pathway; FDFT1 overexpression rescued ATT-induced apoptosis. ChIP assay showed p65 (NF-κB) regulates NEDD4 transcription downstream of FDFT1. |
CETSA, surface plasmon resonance (SPR), molecular docking, siRNA knockdown, overexpression rescue, ChIP assay, flow cytometry, Western blot |
Phytomedicine |
High |
39461203
|
| 2024 |
FDFT1 is transcriptionally regulated by SREBP2 (not SREBP1) in glioblastoma stem cells; FDFT1 activates the AKT pathway to regulate tumor metabolism and maintain stemness. Knockdown of FDFT1 suppressed proliferation, migration, and enhanced temozolomide sensitivity. |
RNA-seq, RT-qPCR, Western blot, siRNA knockdown, FDFT1 inhibitor (YM-53601), neurosphere formation assay, CCK8, transwell/wound healing assays |
Stem cell research & therapy |
Medium |
39707501
|
| 2024 |
microRNA-146b-5p directly targets and downregulates FDFT1 in bladder cancer; FDFT1 suppression redirects its substrate (farnesyl diphosphate) toward the non-sterol branch of the mevalonate pathway, upregulating non-sterol branch genes and reducing total cholesterol, thereby promoting cisplatin resistance via activation of Ras/Rho family protein prenylation. |
Functional knockdown, ectopic overexpression, bioinformatics, rescue experiments, gene expression analysis of downstream pathway |
The international journal of biochemistry & cell biology |
Medium |
39270927
|
| 2025 |
FDFT1 knockdown in HCC decreases cholesterol and bile acid levels, increases HNF4A transcriptional activity, which promotes ALDOB transcription; ALDOB then binds AKT1 and inhibits AKT1 phosphorylation, delaying HCC progression. This HNF4A/ALDOB/AKT1 axis was established as the mechanistic pathway downstream of FDFT1. |
siRNA knockdown, overexpression, in vitro and in vivo experiments, ChIP/promoter binding assays, co-immunoprecipitation (ALDOB-AKT1), AKT inhibitor combination, cholesterol/bile acid quantification |
Advanced science |
High |
39899681
|
| 2025 |
NeuroD1 binds the FDFT1 promoter and activates FDFT1 transcription; this is mediated through KAT2A-catalyzed H3K27 acetylation at the FDFT1 locus, linking NeuroD1-driven histone acetylation to cholesterol biosynthesis in HCC. |
ChIP assay (NeuroD1 binding to FDFT1 promoter), Western blot, RT-qPCR, KAT2A activity assays, loss-of-function/overexpression experiments |
Oncogene |
Medium |
40890513
|
| 2025 |
THEM6 stabilizes FDFT1 protein by interacting with HSP90 to protect FDFT1 from K48-linked ubiquitination and endoplasmic reticulum-associated degradation (ERAD), thereby prolonging FDFT1 protein half-life and increasing intracellular cholesterol biosynthesis; elevated cholesterol from this mechanism decreases ferroptosis susceptibility in TNBC cells. |
Co-immunoprecipitation (THEM6-HSP90, FDFT1 ubiquitination), Western blot, protein half-life analysis, siRNA knockdown, overexpression, in vitro and in vivo (xenograft) functional assays, ferroptosis markers (GPX4, SLC7A11, ACSL4, ROS, MDA) |
Oncogene |
High |
40931051
|
| 2025 |
FDFT1 acts as a negative regulator of autophagy in HCC cells; loss of FDFT1 increased autophagosome formation and lysosomal fusion, while FDFT1 overexpression suppressed basal and induced autophagy through AMPK-ULK1 signaling. |
siRNA knockdown, overexpression, autophagosome imaging, Western blot for AMPK-ULK1 pathway markers |
Biomolecules & therapeutics |
Medium |
42059033
|
| 2025 |
In colorectal cancer, atorvastatin activates the SREBP2-FDFT1 axis (by depleting cellular cholesterol via HMGCR inhibition), and FDFT1-mediated inhibition of the PI3K/AKT pathway induces ER stress, autophagy, and ferroptosis to promote lipid catabolism. |
In vivo AOM/DSS CRC mouse model, Western blot, pathway analysis, FDFT1 overexpression/knockdown |
Cell communication and signaling |
Medium |
41866501
|
| 2024 |
In chicken theca cells, estrogen promotes FDFT1 expression via GSK3β phosphorylation at Tyr216, which enhances binding of GSK3β to LSD1, increasing LSD1Ser54 phosphorylation; elevated LSD1Ser54p then activates FDFT1 transcription, promoting cholesterol biosynthesis. |
CUT&RUN sequencing, transcriptome sequencing, overexpression/knockdown, Western blot, co-immunoprecipitation (GSK3β-LSD1), RT-qPCR |
Biomolecules |
Medium |
39595520
|
| 2025 |
HIV-1 Tat downregulates FDFT1 expression in BCBL-1 cells, reducing cellular cholesterol levels; FDFT1 knockdown upregulates KSHV lytic reactivation genes (ORF50) while FDFT1 overexpression upregulates latency gene (ORF73), establishing FDFT1-mediated cholesterol regulation as a modulator of KSHV replication state. |
Lentiviral overexpression/RNAi knockdown, RT-qPCR, cholesterol assay |
Current HIV research |
Low |
40947702
|
| 2025 |
piR-39980 targets FDFT1, and suppression of FDFT1 leads to inhibition of CYPOR and the EIF3H/HIF1α axis; CYPOR inhibition increases doxorubicin accumulation, and EIF3H/HIF1α axis inhibition induces DNA break-mediated apoptosis, thereby enhancing doxorubicin sensitivity in tongue cancer cells. |
Dual luciferase assay, Western blot, RT-qPCR, flow cytometry, migration assays, molecular assays for CYPOR and HIF1α |
Archives of biochemistry and biophysics |
Medium |
40339976
|
| 2025 |
Squalene synthase (SQS/FDFT1) inhibition in lung cancer cells using pharmacological inhibitors suppressed tumor growth in vivo and reduced lung inflammation and tumor burden, providing evidence that SQS is a functionally important enzyme target in lung cancer. |
In vitro cancer cell assays with SQS inhibitors, in vivo tumor burden and lung inflammation models |
ACS medicinal chemistry letters |
Medium |
41089479
|
| 2025 |
METTL7A directly binds SREBP1 and SCAP, hindering nuclear translocation of SREBP1, thereby reducing expression of FDFT1 (and other cholesterol synthesis genes SQLE, CYP51A1) and intracellular cholesterol content in colorectal cancer cells. |
Co-immunoprecipitation (METTL7A-SREBP1, METTL7A-SCAP), Western blot, immunofluorescence, transcriptomics, proteomics, in vitro and in vivo functional assays |
Cellular oncology |
Medium |
42009961
|