ZNF281 inhibits mitochondrial biogenesis to facilitate metastasis of hepatocellular carcinoma.

ABSTRACT: Zinc finger protein 281 (ZNF281) has been shown to promote tumor progression. However, the underlying mechanism remains to be further elucidated. In this study, ZNF281 knockdown increased the expression of mitochondrial transcription factor A (TFAM) in hepatocellular carcinoma (HCC) cells, accompanied with increment of mitochondrial content, oxygen consumption rate (OCR) and levels of TCA cycle intermetabolites. Mechanistic investigation revealed that ZNF281 suppressed the transcription of TFAM, nuclear respiratory factor 1 (NRF1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Furthermore, ZNF281 interacted with NRF1 and PGC-1α, and was recruited onto the promoter regions of TFAM, TFB1M and TFB2M repressing their expression. Knockdown of TFAM reversed ZNF281 depl

SUBMITTER: Zhao Q 

PROVIDER: S-EPMC10600106 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature