Table 4.

miR‐122 targets genes that are down‐regulated in IR skeletal muscle and adipose tissue

Target	Name	Function	VarElect
			Direct	Indirect
Skeletal muscle (Quadricep, normoglycaemic IR with parental T2D history, Jin et al)
SLC12A1	Solute carrier family 12 member 1	Na/Cl absorption; ionic balance, cell volume	●
PTPN1a	Protein tyrosine phosphatase, non‐receptor type 1	Negative regulator of insulin signalling via dephosphorylating the phosphotyrosine residues of insulin receptor kinase	●
ZNF101	Zinc finger protein 101	Transcription regulation		●
TTL	Tubulin tyrosine ligase	Post‐translational modification of alpha‐tubulin; ligase
MYBa	MYB proto‐oncogene, transcription factor	Transcriptional activator
Skeletal muscle (Quadricep, IR non‐diabetic Pima Indians, Yang et al)
PAPPAa	Pappalysin 1	Metalloproteinase which specifically cleaves IGFBP‐4 and IGFBP‐5, resulting in release of bound IGF	●
PEG10	Paternally expressed 10	Prevents apoptosis in hepatocellular carcinoma; inhibits the TGF‐beta signalling by interacting with the TGF‐beta receptor ALK1		●
CDH6	Cadherin 6	Calcium‐dependent cell adhesion proteins; Wnt signalling		●
MYO9A	Myosin IXA	Actin‐based motor molecules with ATPase activity		●
ENY2	ENY2, transcription and export complex 2 subunit	mRNA export coupled transcription activation
Adipose (Subcutaneous, IR obese, Hardy et al)
PPARGC1B	PPARG coactivator 1 beta	Stimulates activity of several transcription factors and nuclear receptors, including oestrogen receptor alpha, nuclear respiratory factor 1 and glucocorticoid receptor; may be involved in fat oxidation, non‐oxidative glucose metabolism and the regulation of energy expenditure; down‐regulated in pre‐diabetic and T2D patients	●
RPS6KC1	Ribosomal protein S6 kinase C1	Sphingosine‐1 phosphate (SPP)‐mediated signalling		●
GRK3	G‐protein‐coupled receptor kinase 3	Phosphorylates the agonist‐occupied form of the beta‐adrenergic and related GPCRs		●
PEG10	Paternally expressed 10	Prevents apoptosis in hepatocellular carcinoma; adipocyte differentiation; inhibits the TGF‐beta signalling by interacting with the TGF‐beta receptor ALK1		●
Adipose (Omental, IR obese, Hardy et al)
GPD1L	Glycerol‐3‐phosphate dehydrogenase 1‐like	Catalyses conversion of sn‐glycerol 3‐phosphate to glycerone phosphate	●
RSPO1	R‐spondin 1	Ligand for leucine‐rich repeat‐containing G‐protein‐coupled receptors (LGR proteins) and positively regulates the Wnt signalling pathway	●
MYO9A	Myosin IXA	Actin‐based motor molecules with ATPase activity		●
TMTC2	Transmembrane/tetratricopeptide repeat‐containing 2	ER membrane protein; ER calcium homoeostasis		●
GALNT12	Polypeptide N‐acetylgalactosaminyltransferase 12	Catalyses initial step in O‐linked oligosaccharide biosynthesis
GRK3	G‐protein‐coupled receptor kinase 3	Phosphorylates the agonist‐occupied form of the beta‐adrenergic and related GPCRs; carbohydrate metabolism
Adipose (Subcutaneous, IR non‐obese, Keller et al)
DUSP4a	Dual specificity phosphatase 4	Negatively regulates members of the mitogen‐activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation

Predicted miR‐122 targets were compared with down‐regulated genes (≥2 fold, P < .05) in skeletal muscle and adipose tissue samples in 4 reported microarray studies using Gene Expression Omnibus (GEO). Targets that are more likely associated (direct or indirect) with IR‐relevant phenotypes were determined using VarElect (phenotype query: insulin resistance, glucose intolerance, lipid metabolism, type 2 diabetes, glucose metabolism, lipid storage and inflammation).

^aExperimentally verified targets (DIANA‐microT‐CDS). Lists of all overlapped genes from above 5 comparisons are available in Data S3.