HOTAIR is involved in acquired resistance via epigenetic modification of methylation in PTEN, demethylation of TGF- β and cross talk effects from up-and down-regulation of TGF- β and PTEN that enhance the HER2 phosphorylation –independent activity of the MEK/MAPK pathway to promote the proliferation and invasion of tumor cells. This evidence concerns the gene MAP2K7 and neoplasm.