Increased expression of HOTAIR was shown to drive trastuzumab refractoriness in HER-2 positive BC and HOTAIR knockdown resulted in trastuzumab sensitization, and TGF-β, Snail, Vimentin, p-AKT, p-APK, and CyclinD1 suppression, respectively, E-cadherin, PTEN and P27 overexpression [224]. This evidence concerns the gene AKT1 and breast cancer.