Aberrant expression of miR-128 is a frequent observation in human malignancies, but depending on the tumor type, it has been shown to be capable of acting both as an oncomiR and a tumor suppressor miR [22, 23]. Most studies have, however, found it to act as a tumor suppressor and downregulation has been documented in a long list of human malignancies, including glioma, prostate, head and neck, lung and colorectal cancer, where it has been shown to function as an inhibitor of cancer cell growth and metastasis [22, 24–28]. We recently demonstrated that miR-128 regulates another cellular reverse transcriptase, namely the Long-Interspersed Element-1 (LINE-1 or L1) by directly interacting with ORF2 L1 RNA, which encodes L1 RT  and indirectly by regulating a required host factor (Transportin-1 or TNPO1) needed for nuclear import of L1-RNP complexes [29, 30]. De-repression of L1 elements have been demonstrated to function as driver mutations during tumor initiation, as well as during tumor progression [31–37].