high expression of foxm1 critical for sustaining cell proliferation in mitochondrial dnaless liver cancer cells the copy number of mitochondrial dna mtdna is decreased in most cancer types including hepatocellular carcinoma hcc compared to normal counterparts however a decrease in mtdna usually leads to defects in cell proliferation which contradicts the robustness of cancer cell proliferation in this study we found that four out of seven hcc cell lines were of the mtdnaless type interestingly foxm1 a member of the fox transcription factor family was highly expressed in a subset of them with proliferative potential maintained bmyb a partner of foxm1 was also expressed in the same cell lines rnaimediated experiments demonstrated that when foxm1bmyb was silenced in the cell lines cell cyclerelated genes were downregulated while p21cip1 was induced with senescenceassociated galactosidase resulting in g1s cell cycle arrest these results suggest that high expression of foxm1bmyb is critical for sustaining cell proliferation in mtdnaless cells in addition we found that high expression of foxm1 was mediated by the deubiquitinating enzyme otub1 in one cell line thus interference with foxm1bmyb expression such as through otub1 inhibition may induce a dormant state of senescencelike proliferation arrest in mtdnaless cancer cells this finding may be utilized for the development of precision medicine for relevant cancers