While NRF1 is known to collaborate with transcription coactivator PGC1α to regulate target gene transcription in mitochondrial biogenesis, it’s interesting that PGC1α plays a suppressive role in HCC but NRF1 plays a promotive role.[37, 38] Considering that NRF1 can also act as a transcription cofactor of SMAD4 and that PGC1α also functions as transcription coactivator of ERRα, PPARγ etc.,[39] we hypothesize that in HCC the specific transcription pattern makes NRF1 and PGC1α not functionally integrated, which leads to the final difference in their function. This evidence concerns the gene ESRRA and hepatocellular carcinoma.