Table 2.

Roles of some PKM2-associated microRNAs in non-cancer disease.

miRNA	Tissue Expression/Distribution	Research Model	Target Genes/Pathways	Effects on PKM2 Expression	Biological/Physiological Effects	Significance
miR-99a	Liver	Human liver cells (cancerous and noncancerous)	Glycolysis mTOR HIF-1α	Inhibited insulin-induced PKM2 expression	Regulates insulin-induced mTOR and HIF-1α expression Regulates insulin-induced glucose uptake and lactate production [340]	Insulin may inhibit miR-99a to regulate PKM2 expression, which provides a novel biological mechanism of regulating glucose metabolism in the liver that warrants further investigation
miR-122		Chicken livers	Liver metabolism	Inhibition of miR-122 increased PKM2 mRNA level (direct regulation)	Inhibition of miR-122 decreased FABP5 mRNA level [331]	miR-122 may regulate aspects of liver function and homeostasis including lipid and glucose metabolism
		Chicken livers and hepatocytes	Autophagy Oxidative stress	Decreased PKM2 protein levels	Overexpression of miR-122 promoted autophagy and ameliorated arsenic-induced liver damage via decreasing PKM2 levels [341]	Reducing PKM2 expression through promoting miR-122 may lead to novel treatment strategies against arsenic toxicity
miR-19a-3p	Brain	Astrocytes and neurons Cerebral ischemic injury	Glycolysis Apoptosis (Bax, Caspase 3) Adipor2)	Decreased PKM2 protein levels	Decreased glycolytic enzymes, glucose consumption, and lactate production Increased markers of apoptosis [335]	miR-19a-3p may play a role in the regulation of neural cell function and could serve as a potential target against cerebral ischemic injury
miR-143		Ischemic stroke Rat cortex neurons and astrocytes	Glycolysis HK2	Decreased PKM2 mRNA and protein levels	Decreased glucose uptake and lactate production [336]	miR-143 inhibition may have neuroprotective potential during ischemic brain injury (IBI)
	Heart	Endothelial cells	Glycolysis HK2 LDHA	Decreased PKM2 protein levels	Decreased ATP/ADP ratio, glucose consumption, and lactate production [337]	Overexpression of miR-143 may contribute to EC dysfunction through the suppression of glycolytic activity
miR-124		Pulmonary arterial hypertension (PAH)	Proliferation Glycolysis Mitochondrial reprogramming	Decreased PKM2 mRNA levels (indirect regulation mediated through PTBP1)	Decreased glycolysis and lactate production Decreased the proliferation of blood outgrowth endothelial cells (BOECs) from patients with heritable PAH Restored mitochondrial function [338]	Targeting the miR-124-PTBP1-PKM2 axis may be of therapeutic potential for the treatment of PAH
miR125a	Synovium	Psoriatic arthritis (PsA)	Glycolysis Migration Invasion	Suppression of PKM2 expression	miR-125a inhibition promoted EC tube formation, glycolysis, branching, migration, and invasion [342]	Potential therapeutic approach for the treatment of PsA