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BMAL1::CLOCK promotes HCC growth by controlling cell cycle regulators. BMAL1::CLOCK directly activates the transcription of WEE1 but inhibits p21 expression via regulating the REV-ERBs level. Inhibition of BMAL1::CLOCK downregulates WEE1 leading to mitotic catastrophe and apoptosis and elevates p21 level that causes cell cycle arrest. The two mechanisms collaboratively contribute to the pro-proliferative activity of BMAL1::CLOCK in HCC.
