Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma

Abstract

Background and Aims: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PP-P2CA may be involved in HCC were determined using miR-Walk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions: PP-P2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification

“…PP2A (Protein phosphatase 2A) is an indispensable serine and threonine phosphatase that modulates many cellular processes. The PP2Acα (PP2A catalytic subunit Cα, encoded by PPP2CA) is the core enzyme of PP2A, and previous reports revealed that PP2Acα dysfunction plays an important role in the progress of many cancers, such as liver cancer [ 15 ] and acute myeloid leukemia [ 16 ]. Subsequently, the mRNA expression level of PPP2CA is obviously up-regulated in YTHDF2 overexpression cells (HGC27 and MGC803), whereas down-regulated in YTHDF2 knockdown cells (SGC7901 and BGC823) (Fig.…”

Protein phosphatase 2A modulation and connection with miRNAs and natural products

“…miR-548o-3p and miR-200a-3p target PPP2CA liver cancer tissues. 66 miR-520 h enhances breast cancer cell invasion and metastasis by targeting PPP2CA. 67 Arsenic trioxide activates PPP2CA and inhibits the C-X-C motif chemokine receptor 4-mediated metastasis of cervical cancer cells by downregulating miR-520 h. 68 miR-155-5p downregulates PPP2CA to promote interleukin-2 secretion from peripheral blood mononuclear cells in juvenile systemic lupus erythematosus (SLE) patients.…”

“…PPP2CA, a member of PP2A catalytic subunits, is targeted by miR‐548o‐3p, miR‐200a‐3p, miR‐520 h, and miR‐155‐5p in several studies, leading to PP2A inhibition (Table 3). miR‐548o‐3p and miR‐200a‐3p target PPP2CA liver cancer tissues 66 . miR‐520 h enhances breast cancer cell invasion and metastasis by targeting PPP2CA 67 .…”

“…miRNAs are short, single‐strand, non‐coding RNAs (21–23 nt) that target specific genes to downregulate their expressions 55 . Several miRNAs show PP2A‐modulating ability, 23,27,56–85 but the targeting mechanisms warrant a detailed investigation.…”

Developing and Validating an Autophagy Gene-Set-Based Prognostic Signature in Hepatocellular Carcinoma Patients

“…A two-component score 21 was used to semi-quantify IHC staining. Firstly, the staining intensity was assigned a score of 0 (uncolored), 1 (light yellow), 2 (yellow), or 3 (dark yellow).…”