MicroRNA-23b-mediated myristoylated alanine-rich C-kinase substrate suppression (miR-23b-mediated MARCKS suppression)

This target represents a regulatory mechanism where microRNA-23b (miR-23b) negatively regulates the expression of myristoylated alanine-rich C-kinase substrate (MARCKS) protein. MARCKS is a 32 kDa protein that functions as a key regulator of actin cytoskeleton dynamics, membrane trafficking, and cellular architecture[1][2][4]. The protein contains three highly conserved domains: an N-terminal myristoylation site, a MARCKS Homology 2 domain, and a central phosphorylation site domain that serves as the effector domain[1][2]. MARCKS operates through an "electrostatic switch" mechanism, shuttling between the phosphorylated cytosolic form and the unphosphorylated plasma membrane-bound state[1][2][4]. When unphosphorylated, MARCKS localizes to the plasma membrane where it directly binds and cross-links filamentous actin. Upon phosphorylation by protein kinase C or binding to calmodulin, MARCKS translocates to the cytosol[1][4][6]. MicroRNA-23b suppresses MARCKS expression by directly binding to the 3'-untranslated region of MARCKS mRNA[3]. This regulatory relationship is particularly significant in diabetic nephropathy, where miR-23b is downregulated in peripheral blood of diabetic patients and kidney tissues of diabetic animals, while MARCKS expression increases[3]. The miR-23b/MARCKS pathway operates within a complex feedback circuit involving G3BP2, p38MAPK, and p53[3]. In hyperglycemic conditions, decreased miR-23b leads to increased G3BP2 expression, which activates p38MAPK and p53, further suppressing miR-23b expression[3]. Overexpression of miR-23b or inhibition of its downstream targets has demonstrated therapeutic potential in reversing hyperalbuminuria and kidney fibrosis in diabetic models[3]. Conversely, miR-23b antagomir treatment promotes renal fibrosis and increases albuminuria[3]. The pathway also plays roles in cancer biology, endothelial permeability regulation, and inflammatory responses[1][6][10]. MARCKS dysregulation is associated with hematological cancers, inflammatory breast cancer, and therapeutic resistance[1][10].

Other names

miR-23b/MARCKS pathwaymicroRNA-23b targeting of MARCKSmiR-23b-3p-mediated MARCKS regulationmiR-23b/MARCKS regulatory axis

MicroRNA-23b directly binds to the 3'-untranslated region of MARCKS mRNA; Suppresses MARCKS protein expression through post-transcriptional silencing; Regulates MARCKS localization between plasma membrane and cytosol; Modulates downstream actin cytoskeleton organization; Influences protein kinase C-mediated phosphorylation pathways