The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

Abstract

Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3β, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1β, IL-6, JAG2, KCNJ2, MALT1, β-MHC, NF-κB, PCK1, PLCβ1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

“…Signaling pathways include neuronal system [90], GPCR ligand binding [91], metabolism [92] and metabolism of lipids [93] were responsible for progression of AKI. MYH7 [94], BMI1 [95], IGF2 [96], ADORA2A [97], KLK10 [98], MEIS2 [99], IRF7 [100], PRKCB (protein kinase C beta) [101], CCL5 [102], ADAM33 [103], EEF1A2 [104], ACTN3 [105], TRIM65 [106], FCN1 [107], CARNS1 [108], AMH (anti-Mullerian hormone) [109], E2F1 [110], PF4 [111], RPL3L [112], TRIM72 [113], HOXB4 [114], TP73 [115], KCNH2 [116], (advanced glycosylation end-product specific receptor) [117], SMPD3 [118], TYMP (thymidine phosphorylase) [119], RIPPLY3 [120], GREM1 [121], CYP11B2 [122], MYLK2 [123], WNT3A [124], MSX1 [125], COMP (cartilage oligomeric matrix protein) [126], FLI1 [127], ACTA1 [128], TCAP (titin-cap) [129], TUBB1 [130], TNNI3 [131], HSPB7 [132], DES (desmin) [133], RAP1B [134], TNNT1 [135], BHMT (betaine--homocysteine S-methyltransferase) [136], ANGPTL3 [137], CYP3A5 [138], KMO (kynurenine 3-monooxygenase) [139], HMGCS2 [140], AGXT2 [141], FABP1 [142], SLC22A12 [143], CUBN (cubilin) [144], MIOX (myo-inositol oxygenase) [145], FBP1 [146], ARG2 [147], FGF1 [148], CRY1 [149], PPARGC1A [150], UGT1A6 [151], ECHDC3 [152], CYP2C8 [153], ACOX2 [154], SLC2A9 [155], MSRA (methionine sulfoxidereductase A) [156], GC (GC vitamin D binding protein) [157], VNN1 [158], NOX4 [159], GOT2 [160], EPHX2 […”