PPP2R5C (Protein Phosphatase 2 Regulatory Subunit B'Gamma)

MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

B56α mRNA had stronger than predicted secondary structure at their 5' end, and the B56δ/γ splice variants had long regions of weaker than predicted secondary structure at their 5' end. The data suggest that B56α is expressed at relatively low levels as compared to the other B56 isoforms and that the B56δ/γ splice variant is expressed more highly than B56γ/γ.

Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgery. Methylated DNA markers previously identified in sporadic endometrial cancer and colorectal cancer discriminate between benign and cancer tissue in LS.

The results of this study verified that the methylation levels of SDC2, ADHFE1 and PPP2R5C in stool DNA were significantly increased in CRC patients. Combined detection of SDC2/ADHFE1/PPP2R5C methylation is a potential non-invasive diagnostic method for CRC and precancerous lesion screening.

Compared to a national CRC program implemented in Hubei Province between 2018 and 2019 using fecal immunochemical tests and CRC risk assessment questionnaires, current program showed a lower initial positive rate (4.4% vs. 17.4%), higher PPVs for CRC (1.3% vs. 0.08%) in the age-matched group, and a higher adherence rate for colonoscopy (71.3% vs. 18.2%). Conclusions Preliminary prospective evidence suggested that fecal DNA tests had promising diagnostic yield in population-based CRC screening, outperforming FIT/risk assessment questionnaire-based screening strategy.

Our finding reveals that the B56γ3 regulatory subunit-containing PP2A plays an oncogenic role in CRC cells by sustaining AKT activation through suppressing p70S6K activity and suggests that the interaction between B56γ3 and p70S6K may serve as a therapeutic target for CRC. Video Abstract.

Metformin also affects the expression of PPP2R5C, PPP2R5A, and RRAGA, which participate in biological processes such as PI3K-AKT, mTOR, and AMPK signaling pathways. Metformin mediates the expression of related genes to induce apoptosis.

PPP2R5C affects OS metastasis via PI3K/AKT pathway, which may be a potential marker for OS metastasis and recurrence.

Our studies identifies PP2A as a novel regulator of HR and indicates PP2A modulators as a therapeutic therapy for HGSC. In sum, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi-resistance driven by BRCA1/2 mutation reversions.

Together with an oberserved downregulation of phosphorylated-AKT upon miR-193a/b-3p overexpression, this underlines the biological relevance of miR-193a/b-3p downregulation during HPV-induced cervical carcinogenesis. In conclusion, downregulation of miR-193a-3p and miR-193b-3p is functionally involved in the acquisition of HPV-induced anchorage independence by targeting regulators of the PIK3/AKT pathway.

In this direction, inhibition of cell spreading by silencing liprin-α1 is not rescued by expression of B56γ binding-defective liprin-α1 mutant. We propose that liprin-α1-mediated recruitment of PP2A via B56γ regulates cell motility by controlling protrusion in migrating MDA-MB-231 cells.

Moreover, we demonstrate that B56γ-mediated direct dephosphorylation of p-Drp1 inhibited mitophagy and thus increased mitochondria-dependent apoptosis. Overall, our findings demonstrated that activation of B56γ sensitizes the anti-cancer effect of HCC chemoprevention via dephosphorylated regulation of p-Drp1 in inhibiting the interaction between p-Drp1 and Rab7, which may provide a novel mechanism underlying the theranostics for targeting intervention in HCC.

Our results demonstrated that B56γ inhibited HBV/HBx-dependent hepatocarcinogenesis by regulating the dephosphorylation of p-AKT in HCC cells. The intracellular anti-HBx antibody and the activator of B56γ may provide a multipattern chemopreventive strategy against HBV-related HCC.

Furthermore, our findings from the PPI network analysis and eQTL mapping provide supporting evidence of leukemia-associated genes, which can be further explored for their functional importance in leukemia. DATA AVAILABILITY: The myeloid cell transcriptomic data of the BXD mice used in this study can be accessed through our GeneNetwork (http://www.genenetwork.org) with the accession number of GN144.

Down-regulation of PPP2R5C gene expression can inhibit Molt-4 cell activity in childhood acute T lymphocytic leukemia, block the cells in G phase, and promote cell apoptosis, the mechanism may be related to the inhibition of HSP90-GR signaling pathway.

The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.