Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide, and the methods for its treatment have shown limited efficacy. There is an urgent need to explore the underlying mechanism that are involved in hepatocarcinogenesis, contributing to find various signal molecular targets for HCC diagnosis, prevention and therapy. Recently, Various studies have illustrated protein tyrosine phosphatase receptor type D (PTPRD) is an important tumor-suppressor gene that is down-regulated in HCC and this downregulation occurs through its promoter hypermethylation. PTPRD is involved in the progression, migration, apoptosis, invasion and immune suppression of HCC. Also, PTPRD participates in several vital cellular signaling pathways, including PTPRD, signal transduction and activation of transcription 3 (STAT3), JAK, PTPRD, β-catenin, TCF, along with the PTPRD-CXCL8 axis, the PTPRD/phosphatidylinositol3-kinase (PI3K)/mammalian target of rapamycin (mTOR), and the PTPRD/ PD-1/programmed death receptor ligand-1 (PD-L1) axis, thus playing an essential role in HCC. Therefore, PTPRD can be considered as a novel therapeutic target for HCC, and PTPRD-targeted therapeutics in combination with methylation inhibitors, immune checkpoint inhibitors and alternative targeted drugs maybe an innovative treatment method for HCC. However, clinical research of PTPRD-targeted therapies in HCC is greatly limited and tremendous efforts are strongly urged to evaluate its clinical performance in HCC. In this review, we summarized the physiological function and the significant effects of PTPRD and performed a comprehensive analysis of PTPRD-targeted strategies for HCC.

Diffuse large B cell lymphoma (DLBCL) heterogeneity promotes recurrence and anti‐CD20‐based therapeutic resistance. Previous studies have shown that downregulation of MS4A1/CD20 expression after chemoimmunotherapy with rituximab leads to rituximab resistance. However, the mechanisms of CD20 loss remain unknown. We identified that pyruvate dehydrogenase kinase 4 (PDK4) is markedly elevated in DLBCL cells derived from both patients and cell lines with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) resistance. We found that overexpression of PDK4 in DLBCL cells resulted in cell proliferation and resistance to rituximab in vitro and in vivo. Furthermore, loss of PDK4 expression or treatment with the PDK4 inhibitor dichloroacetate was able to significantly increase rituximab‐induced cell apoptosis in DLBCL cells. Further studies suggested PDK4 mediates a metabolic shift, in that the main energy source was changed from oxidative phosphorylation to glycolysis, and the metabolic changes could play an important role in rituximab resistance. Importantly, by knocking down or overexpressing PDK4 in DLBCL cells, we showed that PDK4 has a negative regulation effect on MS4A1/CD20 expression. Collectively, this is the first study showing that targeting PDK4 has the potential to overcome rituximab resistance in DLBCL.

Maintaining the health of the endothelium is of critical importance to prevention against cell aging. The current study was performed to clarify the role of sirtuin1 (SIRT1) in platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endometrial microvascular endothelial cells (HEMECs) was characterized by transmission electron and fluorescence microscopy. Functional experiments were conducted to examine platelet phagocytosis and cell aging using the overexpression or knockdown plasmids of SIRT1 and G alpha-interacting, vesicle-associated protein (GIRDIN) as well as Akt inhibitor and activator. It was found that SIRT1 facilitated platelet phagocytosis by HEMECs, contributing to inhibition of cell aging. Akt activation facilitated platelet phagocytosis and repressed cell aging. GIRDIN overexpression accelerated platelet phagocytosis by HEMECs, leading to a delay in cell aging. GIRDIN phosphorylation at Ser1417 was induced by Akt activation, while activation of Akt was induced by SIRT1-mediated deacetylation, consequently augmenting platelet phagocytosis and delaying cell aging. Taken together, SIRT1 delayed aging of HEMECs by deacetylating Akt, phosphorylating GIRDIN, and inducing platelet phagocytosis. The study highlights a possible target for the prevention of HEMEC aging.

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