IRS1 and Insulin resistance: The reasons are as follows: (1) C/EBPβ, HDAC4 and SOCS1 genes harbor miR-155 binding site, which is conserved across different phyla (Fig 7A and S7A Fig); (2) C/EBPβ[16, 22], HDAC4[23, 24] and SOCS1[25] are negative regulators of blood glucose and insulin sensitivity in mice, and SOCS1 is characterized as a positive mediator of insulin resistance[25]; (3) SOCS1 is a negative regulator of IRS-1/PI3K/AKT insulin pathway[26, 27].