Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) mRNA Expression Is a Prognosis Marker for Hepatocellular Carcinoma

Li, Guang-Bing; Zhang, Xueli; Li, Yuan; Jiao, Qiqi; Liu, Dejie; Liu, Jun

doi:10.1371/journal.pone.0060775

Cited by 21 publications

(15 citation statements)

References 27 publications

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“…PPM1D is a stress-responsive PP2C phosphatase that plays a key role in stress signaling (35). In addition, it was suggested that PPM1D is associated with carcinogenesis (36,37). It negatively regulates the DNA damage response through the dephosphorylation and inactivation of p53, ataxia telangiectasia mutated, p38 and checkpoint kinase 1/2 (38).…”

Section: Discussionmentioning

confidence: 99%

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

et al. 2016

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Cisplatin has been used effectively in the treatment of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) were recently reported to contribute to the pathogenesis and progression of HCC. Their molecular mechanism related to cisplatin treatment remains unclear. The purpose of this study is to identify specific lncRNAs and to clarify their functions in HCC after cisplatin exposure. Reannotation and identification of differentially expressed lncRNAs were performed using the microarray data set GSE38122 in the Gene Expression Omnibus database. Four significantly differentially expressed lncRNAs (RP11-134G8.8, RP11-612B6.2, RP11-363E7.4 and RP1-193H18.2) were identified in HepG2 cells exposed to cisplatin by bioinformatics methods. The upregulated RP11-134G8.8 and RP11-363E7.4 and the downregulated RP1-193H18.2 were confirmed by reverse transcription-quantitative polymerase chain reaction. Furthermore, 57 significant co-expressing genes and their corresponding pathways were annotated and identified. The p53 signaling pathway showed the most significant difference among all pathways. Based on these results, the cell cycle and three key genes, cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21), tumor protein p53 inducible protein 3 (TP53I3) and wild-type p53-induced phosphatase 1 (Wip1, also known as PPM1D), were examined. CDKN1A, TP53I3 and PPM1D were all downregulated by RP1-193H18.2 but upregulated by RP11-134G8.8 and RP11-363E7.4. And obvious S phase arrest was induced by cisplatin treatment for 24 h in HepG2 cells. Finally, the immunofluorescence results showed upregulation of TP53I3 and Wip1 and downregulation of p21 at the protein level. The results suggested that the lncRNAs RP11-134G8.8, RP11-363E7.4 and RP1-193H18.2, and their co-expression genes, which annotated into the p53 signaling pathway, could be potential targets for cisplatin treatment.

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Section: Discussionmentioning

confidence: 99%

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

et al. 2016

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“…A wide range of previous observations also con rmed PPM1D overexpression in mouse embryonic broblasts and in promoting the development of tumors [23][24][25]. Furthermore, in hepatocellular carcinoma, enhanced PPM1D mRNA expression was related to clinical pathological factors and unfavorable prognosis, suggesting as a potential predictor for overall survival of the disease [26]. Yang and his colleagues have also demonstrated that PPM1D was highly expressed in non small cell lung cancer, and associated with the development of this cancer, indicating as an independent prognostic marker [13].…”

Section: Discussionmentioning

confidence: 76%

PPM1D is Associated With Prognosis of Bladder Cancer in the Chinese Population

Cao

Zheng

2020

Preprint

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Background: Present study was to investigate the relative expression and prognostic performance of protein phosphatase magnesium/manganese-dependent 1D (PPM1D) in bladder cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to examine the relative expression of PPM1D mRNA in bladder cancer tissues and adjacent normal bladder tissues. The associations of PPM1D mRNA expression with clinicopathological features and the prognostic value were statistically analyzed via Chi-square test, Kaplan-Meier method and Cox regression analysis.Results: In comparison to adjacent normal tissues, PPM1D mRNA expression was obviously increased in bladder cancer tissues (P<0.001). Abnormal PPM1D expression was remarkably related to histological grade (P=0.017), TNM stage (P=0.032) and lymph nodes metastasis (P=0.035). Kaplan-Meier method showed that a close relationship was found between PPM1D expression and overall survival time (P=0.000). Multivariate analysis indicated that PPM1D expression (P=0.000, HR=3.530, 95%CI: 2.001-6.228) was a promising independent predictor for the prognosis of bladder cancer patients, as well as TNM stage (P=0.042, HR=1.768, 95%CI: 1.021-3.062).Conclusion: Taken together, our data showed that the potential performance of PPM1D as a prognostic biomarker and therapeutic target of bladder cancer.

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“…Notably, high levels of PPMD1 mRNA correlated with tumor size and stage and with poor patient's prognosis. Thus PPMD1 can be considered an interesting potential marker of HCC progression [46] .…”

Section: Protein Phosphatase Magnesium-dependent 1 Deltamentioning

confidence: 99%

Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials

Scaggiante

Kazemi

Pozzato

et al. 2014

WJG

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Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancer-related death. The difficulty to diagnose early cancer stages, the aggressive behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent the reasons for the quite similar deaths per year and incidence number. Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field. Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of (1) molecular and biochemical cellular markers; (2) micro-interfering RNAs; (3) epigenetic variations; and (4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy. In conclusion, we believe that integrated researches among the different lines of investigation indicated above should represent the winning strategies to identify effective HCC markers and therapeutic targets.

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Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) mRNA Expression Is a Prognosis Marker for Hepatocellular Carcinoma

Cited by 21 publications

References 27 publications

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

PPM1D is Associated With Prognosis of Bladder Cancer in the Chinese Population

Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials

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