a, Tetracycline (Tet)-mediated miRNA inactivation or activation by doxycycline administration using Tet-OFF, in which a tissue-specific promoter (TSP) is combined with a transactivator (tTA) to turn on expression of oncogenic miRNA (purple) and induce tumorigenesis (purple star) and subsequent tumour regression, revealing dependence on the oncogenic miRNA, or Tet-ON systems in which a reverse transactivator (rtTA) switches on oncogenic miRNA when the drug is applied. Drug withdrawal leads to tumour regression. b, Tet-mediated miRNA activation or inactivation by doxycycline administration using Tet-OFF or Tet-ON systems. miRNAs (green) can be inhibited by miRNA sponges (dark blue), with the same effects as miRNA expression, leading to tumorigenesis and subsequent tumour regression, which indicates a dependence on tumour-suppressor loss.