HMGA2 and colorectal carcinoma: For instance, let-7 negatively regulates RAS expression through direct binding, which could downregulate MAPK pathway and PI3K/AKT pathway [11, 37]. Let-7 also directly downregulates some oncoproteins such as MYC, HMGA2, and IGF1 [38–41] that are known as critical regulators for the growth of CRC.