ESR1 and breast carcinoma: For example, miR-33b is significantly downregulated in HER2-positive tumors by targeting MYC and downregulating EZH2 [42], miR-21 activates the RAS/MEK/ERK pathway that is crucial in downstreaming signal of HER2-expression in breast cancer cells [43], while miR-4728 is encoded within an intron of HER2 gene and follows HER2 overexpression by targeting EBP1 and ESR1 [44,45].