In this study, we demonstrated that necrosis-inducing peptide P16 kills human glioblastoma cancer cells and primary human hepatoma or renal cancer cells isolated from patients who had not responded to standard treatments.
The expression of FHIT and p16 genes and proteins in HCC tissues were obviously lower than those in cancer-adjacent tissues (P<0.05 in all comparisons).
Furthermore, we found that ribociclib synergized with sorafenib to cause cell death. mRNA analysis of primary human HCC specimens showed that CDK4 expression was correlated with patient survival and that the expression of Rb and the p16-encoding CDKN2A gene were inversely correlated.
As the data suggested, multivariate cox regression analysis revealed that the recurrence-free survival of 46 patients was greatly associated with portal vein tumor thrombus (PVTT) and p16 methylation and receiver operating characteristic (ROC) curves demonstrated that the predictive range of portal vein tumor thrombus (PVTT) combined with p16 hypermethylation was more sensitive than that of either PVTT or p16 hypermethylation alone with regard to disease recurrence in patients with HCC, which could be testified as a valuable biomarker in Clinical application.
Mechanistically, reducing PRC1 blocks mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent manner, and acts synergistically with microtubule-associated agents (MTAs) to suppress p53-wt or p53-null HCC cells in a p53- or p14ARF-dependent manner; while overexpressing PRC1 increases the resistance of HCC to taxol.
Two cases (one nodule-in-nodule case and another case with closely attached HCC and HGDN) showed several overlapped driver mutations (CTNNB1 and CEBPA) and CNAs (losses of CDKN2A, RB1, and TP53) between HGDNs and HCCs, suggesting their roles in the early HCC development.
Compared with paracancerous tissue, normal liver tissue, cirrhosis, and chronic hepatitis B as controls, the pooled ORs of P16 promoter region methylation in HBV-related HCC cancer tissues were 7.18 (95% CI =2.31-22.33), 24.89 (95% CI =3.38-183.03), 5.92 (95% CI =1.78-19.68), and 12.12 (95% CI =0.75-196.50).
<b>Conclusions:</b> HCC pathogenesis affecting p16 methylation don't work during normal blood, when from benign diseases to HCC bloods, can produce powerful role.
Recent studies reported that up-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was found in HCC tissues, and which could affect HCC cells biological processes.
Overall, we observed a high CDKN2A promoter methylation rate (58.18%) in HCC and a significant association between the methylation and HCC risk (OR, 7.07; 95% CI, 5.67-8.80).
Importantly, cirrhotic livers that did not progress to HCC harbor higher expression of the p14ARF protein in hepatocytes compared with that in cirrhotic livers with HCC.
The relationship between the methylation and the clinical features of HCC patients were evaluated.The methylation levels in the 7 CpG loci of p16 gene in HCC patients were low and without statistically significant difference (P > .05) compared to the control groups.
No association was found between p16 methylation or alteration and the prognosis of patients with HCC in overall survival (OS) and disease-free survival (DFS).
Computational Discovery of Niclosamide Ethanolamine, a Repurposed Drug Candidate That Reduces Growth of Hepatocellular Carcinoma Cells In Vitro and in Mice by Inhibiting Cell Division Cycle 37 Signaling.
In vitro experiments using the human HCC cell lines revealed that K19 silencing suppressed cell growth by inducting apoptosis or upregulating p16 and p27, resulting in cellular senescence.
Hotair silence activates P16(Ink4a) and P14(ARF) signaling by enhancing miR-218 expression and suppressing Bmi-1 expression, resulting in the suppression of tumorigenesis in HCC.
Here, we show that knockdown of the farnesoid X receptor (FXR) effectively suppresses the proliferation of human hepatocellular carcinoma cell lines HepG2 and HLE accompanied by elevated expression of cyclin-dependent kinase (CDK) inhibitor p16/INK4a and p21/Cip1 proteins.
HBV infection is associated with p14 (ARF) , p15 (INK4B) , p16 (INK4A) , and RB gene methylation (P = 0.048, 0.035, 0.02); HBV-DNA replication is associated with p14 (ARF) , p15 (INK4B) , p16 (INK4A) , and RB gene methylation (P = 0.048, 0.035, 0.02); high rate of p14 (ARF) , p15 (INK4B) , and p16 (INK4A) in HCC with HBV infection suggests that HBV-induced hypermethylation may be one of the mechanisms of HBV involved in hepatocellular carcinogenesis.
Our results support additional studies incorporating INK4A methylation testing of ccfDNA to further validate the diagnostic, predictive, and prognostic characteristics of this biomarker in HCC patients.