In this study, we examined mRNA expression by quantitative real-time PCR (qRT-PCR) of HOXA10 as well as histone deacetylase (HDAC) and protein levels by Western blot of HOXA10, HDAC1, Cyclin D1, proliferating cell nuclear antigen (PCNA), Survivin and p53 acetylation in HCC tissues and cell lines.
Furthermore, pharmacological or RNAi inhibition of the mevalonate pathway restricts the development of murine hepatocellular carcinomas driven by p53 loss.
Kinases have been targeted for decades with varying results, but the development of therapeutic resistance is a major challenge.<b>Areas covered</b>: The key roles of the RAS/RAF/MEK/ERK, PI3K/PTEN/AKT/mTORC1, TP53 microRNAs (miRs) as therapeutic targets are discussed and we suggests novel approaches for targeting miRs or their downstream targets to combat HCC.
In vitro, Transwell and doxorubicin (DOX)-induced apoptosis assays revealed that GSTM1 showed opposite functions in different HCC cell lines with varied TP53 genotype statuses.
In this study, we report that the haplo-insufficient tumor suppressor ASPP2, a p53 activator, negatively regulates the mevalonate pathway to mediate its inhibitory effect on tumor growth in hepatocellular carcinoma (HCC).
This study highlights the importance of FAT4 and TP53 in HCC pathogenesis and identifies new genetic variants that may have potentials for development of precise therapy for HCC.
Stratifying by the expression of p53 Ser15-P (<i>P</i> = 0.016), but not by p53 (<i>P</i> = 0.301), revealed significantly different survival outcomes in patients with HCC.
It was also found that the most common p53 mutation in hepatocellular carcinomas (R249S) was a much better indicator for poor prognosis than TP53 mutations as a whole.
The HCC-induced group showed a significant decrease in the body mass and a significant elevation in the liver weight, alpha-fetoprotein (AFP), liver enzymes, hepatic malondialdehyde (MDA), and p53 protein expression levels as well as genetic mutations in intron 5 of p53 gene in the form of Single-Nucleotide Polymorphisms (SNPs) and insertions.
To test this hypothesis, the HBV integration sites and the common mutations in the TERT promoter and tumor protein P53 (TP53) coding region were analyzed in 101 HBV-related HCC cases using a capture-next-generation sequencing platform.
Using flow cytometry to determine cell cycle analysis and determination the possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M that lead to inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its ability to increase p53 transactivation.
Small molecules that inhibit MDM2-p53 binding show efficacy against p53 wild-type HCC, but most patients have p53-mutant tumors and intrinsic resistance to such MDM2 inhibitors.
Co-treatment with SB203580, the p38MAPK inhibitor, prevented pro-apoptotic effect of SAC by altering p53 phosphorylation and death inducing signaling complex conformation in HepG2 and induced HCC.
Solasonine-induced apoptosis and cell death of HCC cell lines either expressing p53 (HepG2) or not (Hep3b), indicating that apoptotic activities of solasonine can be mediated not only through p53-dependent but also p53-independent pathways.