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Basic Information

Classification Information

Regulatory Mechanism		Biological Function		Clinical Application
TF		Immune		Survival
Enhancer		Apoptosis		Drug
Variant		Cell Growth		Circulating
MiRNA		EMT		Metastasis
Methylation		Coding Ability		Recurrence

Cancer&Entry Information

Cancer Name	hepatocellular carcinoma
ICD-0-3	C22.0
Methods	qPCR, Western blot, RIP, Luciferase reporter assay etc.
Sample	cell lines (Hep3B, pVSVG-P53, PGFP-V-RS-PKM2 and pGFP-V-RS-Pim1)
Expression Pattern	differential expression
Function Description	we reveal that P53 (N340Q/L344R) promotes hepatocarcinogenesis through upregulation of PKM2. Mechanistically, P53 (N340Q/L344R) forms complex with CUDR and the complex binds to the promoter regions of PKM2 which enhances the expression, phosphorylation of PKM2 and its polymer formation. Thereby, the polymer PKM2 (tetramer) binds to the eleventh threonine on histone H3 that increases the phosphorylation of the eleventh threonine on histone H3 (pH3T11). Furthermore, pH3T11 blocks HDAC3 binding to H3K9Ac that prevents H3K9Ac from deacetylation and stabilizes the H3K9Ac modification. On the other hand, it also decreased tri-methylation of histone H3 on the ninth lysine (H3K9me3) and increases one methylation of histone H3 on the ninth lysine (H3K9me1). Moreover, the combination of H3K9me1 and HP1 a forms more H3K9me3-HP1a complex which binds to the promoter region of Pim1, enhancing the expression of Pim1 that enhances the expression of TERT, oncogenic lncRNA HOTAIR and reduces the TERRA expression.
Pubmed ID	27167190
Year	2016
Title	Double mutant P53 (N340Q/L344R) promotes hepatocarcinogenesis through upregulation of Pim1 mediated by PKM2 and LncRNA CUDR

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