Publication for Hmgcr and Pcsk9

Species	Symbol	Function*	Entrez Gene ID*	Other ID	Gene coexpression	CoexViewer
mmu	Hmgcr	3-hydroxy-3-methylglutaryl-Coenzyme A reductase	15357			[link]
mmu	Pcsk9	proprotein convertase subtilisin/kexin type 9	100102

Pubmed ID	Priority	Text
30940698	0.98	Hmgcr, the other proteins in the cholesterol biogenesis cascade (Fig. S5A) and the low-density lipoprotein receptor (Ldlr), as well as proprotein convertase subtilisin/kexin type 9 (Pcsk9), which antagonizes Ldlr (Fig. 2A), were found in increased abundance during the expansion phase of infection compared to their levels in mock-infected control mice.
	0.98	Hmgcr, Ldlr, and Pcsk9 is regulated by the transcription factor SREBP2, expression of Abca1, Abcg5, and the inducible degrader of the low-density lipoprotein (LDL) receptor (Idol) is regulated by liver X receptor (LXR), transcription factors which are considered to be mutually antagonistic.
	0.96	Hmgcr, Pcsk9, and Ldlr) was not induced until 8 DPI, although the corresponding proteins were found in higher abundance in infected IECs than in controls.
	0.88	Pcsk9 was seen at either expansion phase time points compared to their expression in mock-infected mice, yet a significant increase in the expression of Hmgcr, Ldlr, and Pcsk9 was detected at 8 DPI (Fig. 2D and E).
	0.86	Hmgcr (C), Ldlr (D), Pcsk9 (E), Abca1 (F), Abcg5 (G), and Idol (H) revealed expression levels in IECs enriched from mock-infected or C. rodentium-infected colons.
27707816	0.98	Hmgcr expression by approximately 2-fold relative to vehicle treatment in mice also dosed with control and Pcsk9 siRNA, indicating SREBP transcriptional activation.
	0.95	Hmgcr mRNA and circulating PCSK9 were lower in the statin + Scap siRNA-treated groups relative to vehicle + control siRNA-treated mice, these data demonstrate that inhibition of the HMGCR enzyme and SREBP activation was achieved in the NFR-CETP mice even in the context of Scap mRNA KD.
	0.87	Hmgcr mRNA expression and circulating PCSK9 relative to the vehicle-treated mice in all siRNA-treated mice (control, Scap, and Pcsk9 siRNA treatment groups).
31610608	0.98	HMGCR, LDLR, and PCSK9 (Berger et al., 2017; Hopkins et al., 2019).
	0.98	HMGCR (1.34 Log2 FC), LDLR (1.66 Log2 FC), and PCSK9 (1.63 Log2 FC; Figure 5b).
	0.97	Hmgcr, Pcsk9, and Ldlr did not significantly change up to 6 DPI (although Ldlr showed an initial increase in transcription at 2 DPI) and decreased at 8 DPI, specifically for Hmgcr and Ldlr (Figure 5c-e), suggesting that similarly to C57BL/6 mice, the level of HMGCR, PCSK9, and LDLR protein abundance may be regulated posttranscriptionally (Hopkins et al., 2019).
25931382	0.98	HMG-CoA reductase), the low-density lipoprotein receptor (LDLr) and proprotein convertase subtilisin/kexin type 9 (PCSK9), were clearly upregulated (Fig. 3a) during the post-gavage period.
	0.98	HMG-CoA reductase, the LDLr and PCSK9 were all very rapidly down-regulated, after only 15 min (Fig. 7a).
27892461	0.98	Pcsk9 and Hmgr, while a slight increase in Srebf1c expression was observed (Supplementary Fig. 6I).
	0.97	HMGR, PCSK9 and LDLR mRNA, with maximum effects reaching 1.4, 1.3, 1.5 and 2.3-fold, respectively (Fig. 5f).
28808191	0.98	PCSK9 is regulated by SREBP2, which can lead to a confounding effect of low cellular cholesterol levels leading to upregulation of HMGCR, LDLR (increasing cellular cholesterol levels through endogenous and exogenous pathways) and upregulation of PCSK9 (decreasing cell surface levels of LDLR).
	0.81	PCSK9 may have the most profound effect on LDLR but not HMGCR.
24978143	0.98	HMGCR and PCSK9 compared with mice injected with a control lentivirus.
25378657	0.98	Hmgcr, Hmgcs, Fpps, Ss, Ldlr, and Pcsk9.
25440061	0.98	PCSK9, and HMGCR (Figure 1A).
26567374	0.98	Hmgcr, Ldlr, and Pcsk9 in Mmp2 -/- mice (Figure 3C).
27583452	0.98	Hmgcr and Pcsk9 mRNA levels (Fig 1D and 1E) were upregulated approximately 7- and 9-fold, respectively.
27694328	0.98	Hmgcr, Ldlr, and Pcsk9.
32111832	0.98	Hmgcr, Sqs, Dhcr24, Pcsk9, and Ldlr (Fig. 4c).
28970592	0.97	PCSK9Qbeta-003 vaccine injection was associated with significant up-regulation of sterol-regulatory element-binding protein-2 (SREBP-2), hepatocyte nuclear factor 1alpha (HNF-1alpha), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in LDLR+/- mice.
	0.97	PCSK9 level and up-regulated the level of SREBP-2, HNF-1alpha and HMG-CoA reductase, which indicated that PCSK9Qbeta-003 vaccine also regulated lipid homeostasis.
	0.96	HMG-CoA reductase and increases circulating levels of PCSK9 by as much as 30%, compared with placebo, making them somewhat self-limiting to further reduce LDL-C. This likely occurs because the transcription factor SREBP-2, that is indirectly up-regulated by statin, activates the Ldlr and Pcsk9 genes.
	0.81	Pcsk9 genes, and thus makes statin somewhat self-limiting to further reduce LDL-C. To assess the effect of PCSK9Qbeta-003 vaccine on lipid homeostasis in LDLR+/- mice, we evaluated the mRNA expression of SREBP-2, HNF-1alpha and HMG-CoA reductase in liver.
29404461	0.97	HMGCR and PCSK9.
	0.96	Pcsk9, the expression of SREBP target genes Hmgcr, Acc2, and Scd1 were decreased in the CAT-2003 and combination diet groups but unchanged in the atorvastatin-only group (Fig. 8A-C).
	0.95	HMGCR mRNA expression, which would compound inhibition of de novo cholesterol synthesis, and by blocking the statin-induced up-regulation of PCSK9.
	0.83	PCSK9 that have significant LDL-C lowering effects, represents an alternative choice for combination therapy as they would specifically block the PCSK9 effect of SREBP up-regulation while maintaining the increased expression of LDLR mRNA.35, 36 However, these agents would not inhibit HMGCR mRNA expression.
24647794	0.97	HMG CoA reductase (Fig. 2A), LDL receptors (LDLR) responsible for LDL uptake (Fig. 2B), apolipoprotein B (apoB), a necessary partner for LDL in receptor binding (Fig. 2C), and proprotein convertase subtilisin kexin type 9 (PCSK9) that mediates degradation of the LDLR (Fig. 2D) were unaffected by WD in both mouse strains.
	0.75	HMG CoA reductase, LDLR, apoB and PCSK9 (Fig. 2) was not different from values measured in WT mice, suggesting similar cholesterol synthesis and LDL uptake.
24695360	0.97	Pcsk9, Hmgcr and Hmgcs (see Table 2 and Figure S2).
24768901	0.97	Hmgcr, Pcsk9) (Fig. S1A).
26023080	0.97	Pcsk9, Srebp-1c and Srebp-2, and their other targets, fatty acid synthase, stearoyl CoA desaturase 1 (Scd1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr) and farnesyl diphosphate synthase (Fdps), were decreased by 44-98% in streptozotocin treated mice.
28178673	0.97	PCSK9 knockdown resulted in an increase in IDI1 and HMGCR levels in both acRoots-treated and untreated LM3 cells (Figure 6L and 6M).
28244871	0.97	HMG-CoA reductase, farnesyl diphosphate synthase, squalene synthase, and PCSK9) were reduced by 60-80% in hepatocyte-Srebf-2-/- livers compared to controls.
29084592	0.97	HMG-CoAr (+ 5.4-fold of CH), SCAP (+ 1.7-fold of CH), and PCSK9 (+ 1.4-fold of CH) compared with the CH group (Fig. 2a).
23510830	0.96	hydroxylmethylglutaryl-CoA reductase (HMGCR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes would be affected in liver tissues of AdR1-TG mice since these molecules play important roles in cholesterol homeostasis for lipid metabolism.
	0.74	HMGCR and PCSK9, in liver of AdR1-TG mice were detected with significant downregulations; SREBP-1 was decreased on average 72% (p < 0.01), HMGCR was decreased on average 75% (p < 0.01), and PCSK9 was decreased on average 82% (p < 0.01) when expression of these genes was compared with the results from control WT mice.
30582457	0.96	Pcsk9, Hmgcr or Srebf2 (Figure 6D-F).
	0.94	PCSK9 (185 +- 28 ng/ml vs. 112 +- 15 ng/ml) and total cholesterol levels (142 +- 15 mg/dl vs. 101 +- 8 mg/dl) decreased without a change in the mRNA levels of hepatic Pcsk9, Hmgcr or Srebf2 (Online Figure X).
20498851	0.96	PCSK9 mRNA, with no observable effects on the mRNA expression levels of LDLR and HMGCoAR.
30354208	0.94	Pcsk9 and Hmgcr were unaffected by OCA.
29535632	0.93	PCSK9, LXRalpha, and ABCA1, and had no significant effect on gene expression of HMGCR and CYP7A1 in HepG2 cells.
	0.80	HMGCR, LDLR, PCSK9, LXRalpha, CYP7A1, and ABCA1 in HepG2 cells.
	0.65	HMGCR, (B) LDLR, PCSK9, (C) ABCA1, CYP7A1, and LXRalpha in HepG2 cells.
24158514	0.93	HMGCR, PCSK9) in mouse primary hepatocytes were not affected by Ad-shHNRNPD infection (Figure 5C), thus confirming the specific targeting effect of the shRNA to hnRNP D. The reduction of hnRNP D by Ad-shHNRNPD transduction with a consequential increase in LDLR protein level was also observed in mouse hepatoma-derived cells (Figure 5D).
29404516	0.92	3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Hmgcr), low-density lipoprotein receptor (Ldlr), and proprotein convertase subtilisin/kexin type 9 (Pcsk9, an inhibitor of Ldlr) but had no effect on angiopoietin-like 3 (Angptl3, lipoprotein lipase inhibitor) or Srebp2 (cholesterol synthesis regulator) compared to wild-type mice.
32027669	0.91	Hmgcr, Sqle) and fatty acids (Fasn, Scd1), but also direct cholesterol transport (Ldlr, Pcsk9, Stard4) and retinoid synthesis (Aldh1a1, Rdh11).
25799309	0.89	Hmgcr, Sqle, Cnbp, Dhcr24, Nsdhl, Fdps, Sc4mol, Fdft1 and Tm7sf2), cholesterol transport and uptake (e.g., Cd36, Apoa4 and Ldlr), cholesterol homeostasis (e.g., Fabp4, Apoa4, Pcsk9 and Ldlr), triglyceride synthesis (Ces3, Ppap2a, Dgat2, Ppap2c and Pcsk9) and triacylglycerol catabolism (Lpl and Gk2) (Fig. 4A, Fig. 5E, F and S7-S8 Tables), indicating that the decreased expression of these hepatic genes involved in cholesterol and triglyceride metabolism might be responsible, or contribute to the decreased cholesterol and triglyceride levels observed in Rm155LG/Alb-Cre transgenic mice.
26467524	0.69	hmgcr (3-hydroxy-3-methylglutaryl-CoA reductase): see Fig. 3b; and those encoding low-density lipoprotein receptor related proteins, pcsk9 (proprotein convertase subtilisin/Kesin type 9) and lpr1 (low density lipoprotein receptor-related protein 1).
29406859	0.68	3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors and the novel proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have helped to lower the incidence of CVD, a substantial part of the population still have CVD.
22538429	0.55	PCSK9, APOB, LDLRAP, and IBCG5/8 for LDL-C. GWAS have also identified genes that are drug targets for LDL-lowering therapies, including NPC1L1, the molecular target of ezetimibe, and HMGCR, the molecular target of statin drugs .