Publication for HMGCS1 and SREBF2

Species	Symbol	Function*	Entrez Gene ID*	Other ID	Gene coexpression	CoexViewer
hsa	HMGCS1	3-hydroxy-3-methylglutaryl-CoA synthase 1	3157			[link]
hsa	SREBF2	sterol regulatory element binding transcription factor 2	6721

Pubmed ID	Priority	Text
25313139	0.98	SREBP2, HMGCS and HMGCR, suggesting that the latter two inhbitors stimulate cholesterol synthesis in LNCaP cells through a feedback mechanism.
	0.97	SREBP2 regulates the expression of hydroxy-methyl-glutaryl-CoA synthase (HMGCS) and hydroxy-methyl-glutaryl-CoA reductase (HMGCR), two key enzymes of cholesterol synthesis.
	0.97	SREBP2, HMGCS, and HMGCR by qRT-PCR (Fig. 2C).
	0.97	SREBP2, HMGCS and HMGCR expression was analyzed as in A.
	0.96	SREBP2, HMGCS and HMGCR) by orlistat and TOFA but not TCS and C75.
22154237	0.98	SREBP2-mediated upregulation of the 3-hydroxy-3-methylglutaryl-Coenzyme A synthase (HMGCS1) upon sterol depletion, respectively.
	0.96	HMGCS1, indicating efficient blocking of SKI-1/S1P-mediated cleavage of ATF6 upon ER stress and SREBP2 induced by cholesterol depletion (Fig 1A).
	0.94	SREBP2-mediated upregulation of the 3-hydroxy-3-methylglutaryl-Coenzyme A synthase (HMGCS1).
32028644	0.98	SREBF2, HMGCR, and HMGCS1, while in contrast, their expressions were significantly reduced by the 25-HC treatment (Figure 5A-C).
	0.97	SREBF2 (A), HMGCR (B), and HMGCS1 (C) was analyzed in BIX- and 25-hydroxycholesterol (25-HC)-treated H1299 cells.
	0.95	SREBF2, along with HMGCR and HMGCS1, was also increased after BIX treatment in A549 (Figure 4E).
18307821	0.98	SREBF2, MBPTS1, SCAP, LDLR and HMGCS1 is involved in lipid metabolism.
29712938	0.98	HMGCS1), CETP, and PCSK9, which are regulated by SREBP-2, might be responsible for cholesterol lowering effects by sauchinone.
26353928	0.97	HMGCS1, GGPS1 and SREBP2 (Figure 1A and 1D).
	0.94	3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), and SREBP2.
	0.94	HMGCS1, GGPS1 and SREBP2, using two unique shRNA's for each target.
	0.94	SREBP2 plays a central role in the MVA pathway as a master transcriptional activator of sterol responsive genes including HMGCS1 and HMGCR.
	0.89	sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) and geranylgeranyl diphosphate synthase 1 (GGPS1).
	0.87	SREBP2 knockdown in lung and breast cancer cells completely abrogated the fluvastatin-induced upregulation of sterol-responsive genes HMGCR and HMGCS1.
	0.80	SREBP2 is cleaved and translocates to the nucleus, where it induces the transcription of sterol-responsive genes such as HMGCR and HMGCS1.
	0.78	SREBP2, GGPS1 and HMGCS1 can potentially perturb other pathways in addition to the MVA pathway.
	0.75	SREBP2, GGPS1 and HMGCS1) can potentiate statin-induced apoptosis in A549 cells.
31540279	0.97	HMGCS1 and SREBP2 under normal cholesterol conditions (Figure 3C).
	0.93	HMGCS1, HMGCR, FDPS, and MVD, which are tightly regulated by an SREBP2 transcription factor.
	0.91	sterol regulatory element-binding protein 2 (SREBP2) enrichment indicating transcriptionally active regions of 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), farnesyl diphosphate synthase (FDPS), and mevalonate diphosphate decarboxylase (MVD).
	0.81	HMGCS1, Sterol regulatory element-binding protein 2 (SREBP2), and HMGCR, in SK-HEP-1 cells (Figure 3A).
	0.54	HMGCS1 and SREBP2, as well as the heat shock-responsive gene HSPA6, were observed (Figure 3D).
22754327	0.97	SREBP-2 gene expression, and reduces expression of its own target genes, such as HMGCS and HMGCR, then down-regulates cholesterol biosynthesis in the liver.
	0.64	SREBP-2 primarily regulates cholesterol metabolism by activating genes required for cholesterol biosynthesis such as HMGCS, HMGCR, farnesyl diphosphate synthase, and squalene synthase.
26535009	0.97	SREBP-2 predominantly activates genes involved in cholesterol metabolism (including HMGCR, HMGCS1, and LDLR) .
	0.56	SREBP-2 cleavage through ERBB kinase activity but independent of AKT and mTORC1 resulting in increased expression of cholesterogenic genes (including HMGCR, HMGCS1, and LDLR) and increased LDL uptake and cholesterol synthesis.
26938778	0.97	HMGCS1 (Entrez Gene: 208715), HMGCR (Entrez Gene: 15357), MVD (Entrez Gene: 192156), SQLE (Entrez Gene: 20775), and SREBF2 (Entrez Gene: 20788) in CH25H -/- cells treated with interferon gamma (IFN-gamma) (UniProt: P01580).
	0.94	SREBF2) and 24 h (HMGCS1, HMGCR, MVD and SQLE) after addition of the cytokine.
32161285	0.97	HMGCS, but had no effect on expression of genes involved in SREBP2 maturation, including SCAP and PAQR3 (Fig. 4f).
	0.88	SREBP2 dissociates from Insig and trafficks to the Golgi, where the two proteases site-1 protease (S1P) and site-2 protease (S2P) promote SREBP2 processing, leading to translocation of the mature form of SREBP2 to the nucleus where it induces the expression of genes involved in cholesterol uptake and synthesis, including LDLR, hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and HMGC synthase (HMGCS).
31159817	0.97	HMGCS1, log2FC = 2, P = 9.7 x 10- 19), which catalyzes the first step of the cholesterol biosynthetic pathway to generate HMG-CoA from acetyl-CoA. As expected, the gene encoding for the primary target of statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR: log2FC = 1.7, P = 1.1 x 10- 14) was upregulated in statin-treated patients due to the well-known counter-regulation effect mediated by sterol regulatory element-binding protein-2 (SREBP2) (Additional file 1: Figure S3).
31604910	0.97	SREBP2 binding was observed at promoters of the major targets such as HMGCS1, MVK, SQLE, and DHCR24 in ChIP-seq and ChIP-qPCR analyses (Fig. 4f top, Supplementary Fig. 4c, d top).
25933205	0.96	SREBP-2 is a key transcription factor that regulates HMGCR and HMGCS expression.
	0.96	SREBP-2 was accompanied by a significant decrease in HMGCR mRNA expression and a slight decrease in HMGCS mRNA expression; this disparity may derive from the differential effects of SREBP-2 in stimulating target gene transcription.
	0.95	SREBP-2 protein levels, the TSH-mediated up-regulation of HMGCR and HMGCS mRNA expression was attenuated by AICAR in HepG2 cells (Fig 4E).
	0.94	SREBP-2 precursor and nuclear active forms as well as the HMGCR and HMGCS target genes were significantly up-regulated by TSH in HepG2 cells, which was consistent with our previous findings.
	0.93	Sterol regulatory element-binding protein-2 (SREBP-2) is synthesized as a precursor protein in the endoplasmic reticulum and subsequently undergoes sequential proteolytic cleavage to attain the N-terminal transcriptionally active form; the active form translocates into the nucleus to promote the expression of target genes involved in cholesterol biosynthesis and uptake in the liver, such as 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and low-density lipoprotein receptor (LDLR).
	0.80	SREBP-2 protein levels and the expression of its target genes, HMGCR and HMGCS, in HepG2 cells.
	0.71	SREBP-2 and its target genes HMGCR and HMGCS, which are key enzymes in cholesterol biosynthesis, and suppressed the TSH-stimulated up-regulation of SREBP-2 in HepG2 cells; similar results were obtained in TSH receptor knockout mice.
29226804	0.96	SREBP2 target proteins FDFT1, HMGCS1, and IDI1 in Huh7 cells (Table S1; Figures 3E and 4B), and showed a trend for increased expression of other cholesterol synthesis enzymes in HepG2, HEK293, and HeLa cells (Table S1; Figures 3E and 4B).
	0.96	HMGCS1, FDFT1, and FDPS) were not generally high or low in any cell line (Figure 5A), suggesting that the variable basal expression was not just the result of variable activity of SREBP2.
	0.95	HMGCS1 activity did not activate SREBP2 indicated that HMGCS1 is not a rate-limiting enzyme in this pathway, a finding in agreement with the general view that HMGCR catalyzes the committing and first rate-limiting step.
	0.92	SREBP2 on HMGCS1 the curves indicate that the strength of these functional interactions is similar across all cell lines (Figures 7A and 7B).
25070550	0.96	SREBP2 or SREBP2 target genes, HMGCR, HMGCS, SS, LDLR or PCSK9 (Supplementary Table 1).
	0.95	HMGCS and SS, but not other SREBP2 target genes, were significantly reduced in PCSK9 siRNA transfected enterocytes compared with control cells treated with a scrambled siRNA control vector.
	0.90	SREBP2 mRNA levels, PCSK9 siRNA produced significant reductions in SREBP2 target genes involved in cholesterol biosynthesis, HMGCR, HMGCS and SS (Figure 3E).
27308369	0.96	HMGCS1, HMG-CoA synthase 1; SREBP2, sterol regulatory element binding transcription factor 2; FPP, farnesyl pyrophosphate; GGPP, geranaylgeranyl pyrophosphate; LDLr, low-density lipoprotein receptor.
	0.88	SREBP2 into the nucleus (2), and the ensuing transcription of sterol-responsive genes including HMGCR, HMGCS1, and LDLR, thereby blunting the anticancer efficacy of statins in tumor cells (3).
28526856	0.96	SREBP2, HMGCR, HMGCS, LDLr) and efflux (ABCA1, ABCG1, ABCG5, NPC1, NPC2) gene expression.
	0.86	SREBP2, HMGCR and HMGCS were all upregulated 2.5-3-fold (P < 0.001), while LDLr was upregulated nearly 5-fold (P < 0.001, Fig. 3).
24493696	0.96	SREBP-2 is a master transcription regulator that up-regulates several key cholesterogenic genes, such as HMGCS1, HMGCR and LDLR.
26632252	0.96	SREBP2, HMGCS1, HMGCR, LDLR, ABCA1, ABCG1, ABCG5, ACACA, FASN and CYP27B1 after over-expression or depletion of hsa-miR-195 in MCF-7 cells using real time PCR analysis (Fig. 3B).
31098406	0.96	sterol response element binding protein 2 (SREBP2) downstream genes (SREBP2, HMGCS1, HMGCR, and FPP) in HepG2 cells (n = 3).
31561416	0.95	SREBP2 and its target genes related to cholesterol biosynthesis, such as HMGCS1, HMGCR, MVD, and FDPS, in order to increase intracellular cholesterol levels.
	0.90	SREBP2 maturation is induced, followed by its translocation into the nucleus for activation of its target genes, including those encoding hydroxymethylglutaryl (HMG)-CoA synthase 1 (HMGCS1), HMG-CoA reductase (HMGCR), farnesyl diphosphate synthase (FDPS), and mevalonate diphosphate decarboxylase (MVD), for de novo cholesterol synthesis.
	0.82	HMGCS1, HMGCR, MVD, FDPS, and SREBP2), fatty acid synthesis (SREBP1a and SREBP1c), and cholesterol uptake (LDL-R) in UA-treated SK-HEP-1 cells, and this UA-induced gene expression was similar to that observed with simvastatin treatment (Figure 2A).
	0.74	HMGCS1, and SREBP2 was observed in UA-treated SK-HEP1 and Hep3B cells (Figure 2B).
30561264	0.95	HMGCS1, 3-hydroxy-3-methylglutaryl-CoA synthase 1; LCAT, lecithin-cholesterol acyltransferase; LDLR, low-density lipoprotein receptor; LSD, least significant difference; MTTP, microsomal triglyceride transfer protein; NPC1L1, NPC1 like intracellular cholesterol transporter 1; PCSK9, proprotein convertase subtilisin/kexin type 9; SOAT2, sterol O-acyltransferase 2; SREBF2, sterol regulatory element binding transcription factor 2.
	0.74	sterol regulatory element binding transcription factor 2 (SREBF2) by 2-fold, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR; 3.5- and 4-fold, respectively), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1; 5.5- and 6.5-fold, respectively), low-density lipoprotein receptor (LDLR; 3.5- and 2-fold, respectively), and proprotein convertase subtilisin/kexin type 9 (PCSK9; 3.5- and 2-fold, respectively; Figure 8A and Table 3).
32033570	0.94	SREBP2 into the nucleus, and the ensuing transcription of sterol-responsive genes including HMGCR, 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), mevalonate diphosphate decarboxylase (MVD), and SQLE, thereby facilitating the cholesterol synthesis and changing the invadopodia cell membrane fluidity (Fig. 7b).
	0.83	SREBP2 protein expression level as well as its downstream targets, HMGCS1, HMGCR, MVD, SQLE were all deregulated by HADHA.
27648077	0.93	SREBP2, 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), HMG-CoA reductase (HMGCR), farnesyl diphosphate synthase (FDPS), Cytochrome P450 Family 51 Subfamily A Polypeptide 1 (CYP51A1), and 7-dehydrocholesterol reductase (DHCR7) mRNA levels (Figure 5(b)).
	0.93	SREBP2, HMGCS1, HMGCR, FDPS, CYP51A1, and DHCR7, were quantified by RT-qPCR analysis.
24619155	0.92	SREBP-2, HMGCR, HMGCS, and LDLR in NPC1 cells after incubation with HP-beta-CD (beta-CD: 10 mM) or HE-SS-PRX (beta-CD: 0.2 mM) for 24 h at 37 C. Data are normalized to the expression level of beta-actin.
	0.91	SREBP-2 processing and upregulating the expression level of mRNAs related to cholesterol biosynthesis and uptake, such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS), and low-density lipoprotein receptor (LDLR).
	0.85	SREBP-2, HMGCR, HMGCS, and LDLR in NPC1 cells were evaluated after treatment with HE-SS-PRX or HP-beta-CD (Fig. 4B).
31023626	0.92	HMGCS1 expression in response to fluvastatin was not due to a lack of SREBP2 expression (Figure 3D).
	0.91	SREBP2 knockdown abrogated fluvastatin-induced HMGCS1 expression and significantly decreased the IC50 value of fluvastatin (Figure 4D-E).
31685796	0.91	SREBP-2 transcriptional activity, we generated luciferase reporter constructs containing the hamster HMGCS1 promoter, the human LDLR promoter, or three sterol regulatory elements (3SRE) that bind SREBP-2.
30584280	0.89	SREBP-2 protein levels, there was a sharp decline in the levels of the SREBP-2 downstream target proteins HMGCR and HMGCS by metformin treatment.
	0.83	SREBP-2 expression and decreased the level of its target proteins HMGCR and HMGCS; DN-AMPK attenuated the cholesterol-lowering effect of metformin, which is obvious evidence suggesting that metformin effects are primarily mediated by AMPK.
23085030	0.89	SREBF2, HMGCS1, INAIG1, IDI1, CYP1B1 and IGFBP3 were analyzed for the 4-day exposure.
31592021	0.89	SREBP2 and its downstream gene HMGCS1.
30321984	0.88	SREBP-2 transcriptionally activates the expression of cholesterogenic genes in cholesterol-depleted conditions, such as hydroxymethylglutaryl (HMG)-CoA synthase 1 (HMGCS1), HMG-CoA reductase (HMGCR), farnesyl diphosphate synthase (FDPS), and mevalonate diphosphate decarboxylase (MVD).
30580964	0.82	HMGCS1, and SREBF-2 was assessed by qRT-PCR (n = 3; *p < 0.01; n.s., not significant).
23324130	0.79	SREBF2 and INSIG2 and up-regulation of INSIG1, HMGCS1 and HMGCR in moxLDL-SMC indicates the initiation of cholesterol synthesis in the 3h moxLDL-SMC cells.
25563794	0.77	SREBP2, which activates the expression of genes required for cholesterol biosynthesis, including HMGCS, HMGCR, LDLR, farnesyl diphosphate synthase, and squalene synthase.
18959802	0.75	Hmgcs1), HMG CoA reductase (Hmgcr), sterol receptor binding factor-2 (Srebf2) and lanosterol 14 alpha-demethylase (Cyp51a1) (involved in cholesterol metabolism), and others including fatty acid synthase (Fasn), fatty acid binding protein (Fabp), farnesyl diphosphate synthase (Fdps), acetyl-coA carboxylase (Acaca), acetyl-coA dehydrogenase (Acadm), acetyl-coA acetyl transferase (Acat2), peroxisome proliferative activated receptor, gamma (Ppargamma) and a variety of apolipoproteins that are involved in fatty acid and triglyceride metabolism.
30970006	0.54	SREBF2-depleted group there is no significant elevated expression of DNCS genes, HMGCS1 and HMGCR, in 1% ITS medium compared to 0% FBS (Fig 4A and 4B, statistical comparisons marked in green).
31497741	0.54	SREBP-2 positively induces the expression of the enzymes for cholesterol synthesis and uptake, HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGCS), and LDLR.39 In line with the TC and FC accumulation, our gene and protein analysis revealed that the I148M PNPLA3-carrying HSCs displayed lower SREBP-2 transcriptional activity in both primary and overexpressing cells, as suggested by decreased LDLR, HMGCR, and HMGCS expressions (Fig. 2D,E; Supporting Figs. S1 and S2).
20531405	0.53	SREBP2 activation, which ultimately reduces transcription of HMGCR and HMGCS, as well as many other SREBP2-dependent genes.
31448116	0.51	HMGCS1) and transcription of lipid genes (SREBF2) in FH subjects compared with controls.