PLEKHA4 (Pleckstrin Homology Domain Containing A4)

We evaluated the effects of PLEKHA4 knockdown combined with temozolomide (TMZ) on glioblastoma cell proliferation and apoptosis in vitro and in vivo...Knocking down PLEKHA4 combined with TMZ inhibited cell proliferation and promoted cell apoptosis in vitro and in vivo. Our results indicated that HOXD9-medicated PLEKHA4 regulates glioblastoma cell proliferation and glycolysis via activation of the STAT3/SOCS1 pathway.

The present findings suggested that PLEKHA4 could promote melanoma cell proliferation by regulating both the MAPK and Wnt/β‑catenin pathways, thereby proposing PLEKHA4 as a promising therapeutic target for MM. Further studies are warranted to elucidate the mechanisms underlying PLEKHA4‑mediated modulation of cMyc ubiquitination.

Notably, overexpression of PLEKHA4 activated Wnt/β‑catenin signaling, reinforcing its role in promoting β‑catenin nuclear translocation and signaling activity. The present findings suggested that PLEKHA4 could serve as a potential therapeutic target for KIRC; inhibiting PLEKHA4 or modulating Wnt/β‑catenin signaling could provide new avenues for treatment strategies in KIRC.

The findings indicate that PLEKHA4 is an independent prognostic biomarker associated with key signaling pathways and immune infiltration in BC. Targeting PLEKHA4 may contribute to improving immunotherapy for BC.

In addition, the in silico data of scRNA-seq showed high expression of these genes in several cell types of normal breast tissue, including breast myoepithelial cells and smooth muscle cells. Thus, our results suggest their possible tumor-suppressive function in breast cancer and muscle development.

Our findings highlight the pivotal role of PLEKHA4 in GBM pathogenesis and suggest its potential as a diagnostic and therapeutic target for GBM.

Additionally, we found that PLEKHA4 expression was closely associated with drug sensitivities and immunotherapy responses, indicating that PLEKHA4 expression also had potential clinical significance in guiding immunotherapy and chemotherapy in LGG. PLEKHA4 plays a pivotal role in reshaping the TME of LGG patients, and may serve as a potential predictor for LGG prognosis and therapy.

PLEKHA4 is highly expressed in glioma tissues and correlated with tumour stemness, immune cell infiltration and proliferation, suggesting its potential as a novel prognostic biomarker and therapeutic target in glioma.

We recommend quantitative phosphoproteomics in early-stage primary hepatic carcinoma, which offers great promise for in-depth insight into the molecular mechanism of early-stage primary hepatic carcinoma, the discovery of effective therapeutic targets/drugs, and the construction of reliable phosphorylation-related biomarkers for patient stratification, predictive diagnosis, prognostic assessment, and personalized medical services in the framework of PPPM. The online version contains supplementary material available at 10.1007/s13167-023-00335-3.

PLEKHA4 knockdown inhibited the proliferation of glioma cells and promoted apoptosis by inhibiting the activation of the MAPK signaling pathway and expression of β-catenin. Lactic acid produced by glycolysis upregulates the expression of PLEKHA4 in glioma cells.

Our findings proposed that PLEKHA4 was an independent prognostic biomarker and correlated with immune infiltrates in glioma, and targeting PLEKHA4 might improve immunotherapy in glioma. Of course, these findings also need basic experiments and further clinical trials to confirm in the future.

According to functional enrichment analysis, PLEKHA4 levels in LGG are associated with immune infiltration and immunotherapy. In conclusion, PLEKHA4 is a potential prognostic marker and immunotherapy target for LGG.