HLPP2 (PH Domain And Leucine Rich Repeat Protein Phosphatase 2)

Furthermore, lncRNA ILF3-AS1 was identified as an independent predictor of metastatic CRC. These findings suggest that circPHLPP2 and lncRNA ILF3-AS1 could serve as promising biomarkers for the diagnosis and staging of CRC.

Clinically, our analysis of 91 TNBC patients who received cisplatin-based neoadjuvant chemotherapy found that high ATP6V0D2 expression was inversely correlated with pathological complete response (pCR), whereas PHLPP2 levels showed positive association, supporting the proposed mechanistic link. Together, these findings highlight the impact of ATP6V0D2 on TNBC progression and cisplatin sensitivity, nominating ATP6V0D2 as a promising therapeutic target.

Functional assays showed that TRIM46 promoted cisplatin (CDDP) chemoresistance...In summary, our study reveals that TRIM46 promoted chemoresistance via downregulating PHLPP2, leading to activating PI3K/AKT pathway. This study provides a novel potential target for ovarian cancer therapy.

Notably, targeting FBXO32 significantly inhibited tumor growth in both an orthotopic HCC model and an organoid model derived from HCC patients. To sum up, this work emphasizes the part of FBXO32 in propelling HCC progression via facilitating PI3K-AKT pathway activation via PHLPP2 degradation.

Gene expression signatures associated with late PDX passages (3rd-5th) were enriched with proliferation and metabolic reprogramming-related genes and predicted prognosis in an independent AITL series. Low PHLPP2 mRNA expression predicted poor prognosis (p = 0.05) and engineered PHLPP2 or TET2 loss in CD4+ T-cells showed enhanced PI(3)K activation, thus uncovering a therapeutic target for clinical trials.

This suppression led to lower levels of p27, FOXO3a and p21, thereby enhancing the proliferation of HCC cells by relieving the negative regulatory mechanisms of the cell cycle. This research offers significant understanding into the oncogenic pathways induced by Cr(VI), and provides laboratory evidence for mechanistic studies targeting hepatic carcinoma associated with Cr(VI) exposure.

Finally, using phylogenomics, we identify coevolving genes consistent with a scaffolding role for PHLPP2 on membranes. In summary, our results provide a molecular explanation for the inconclusive results that have hampered research on PHLPP and argue for a focus on the noncatalytic roles of PHLPP1 and PHLPP2.

Exosomal miR-188-3p derived from CRC cells can promote liver metastasis by activating HSCs to form a PMN through targeting PHLPP2 to activate the AKT/mTOR pathway. These results offer a new perspective on the mechanisms driving CRLM.

Mechanistic studies reveal that VDR regulates METTL14 expression via promoter binding, modulating key target genes such as SOX4, DROSH, and PHLPP2. This study highlights the role of the VDR-METTL14 axis as a protective mechanism in CAC and suggests its potential as a therapeutic target for preventing and treating CAC.

Overall, our findings reveal a novel mechanism by which circRNA regulates CRC immune evasion. circPHLPP2 may serve as a prognostic biomarker and potential therapeutic target for CRC patients.

A deeper understanding of these mechanisms may unveil potential targets for early diagnosis, prognosis assessment, and dietary recommendations for pancreatic cancer. These findings hold clinical significance not only for pancreatic cancer but also for other malignancies exhibiting heightened ZIP4 expression.

Our study reveals that miR-25-3p from hypoxic glioma cells is delivered to macrophages via exosomes as a mediator, promoting M2 polarization of macrophages through the miR-25-3p/PHLPP2/PI3K-AKT signaling pathway. This study suggests that targeted interventions to modulate miR-25-3p expression, transmission, or inhibition of PI3K-AKT pathway activation can disrupt the immune-suppressive microenvironment, providing a novel approach for immunotherapy in gliomas.