Fan Yao

Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene. However, recent reports have indicated that HPRT1 overexpression is associated with a poor prognosis in various types of cancers. Using The Cancer Genome Atlas (TCGA), HPRT1 was found to be highly expressed in various cancer types, especially in head and neck squamous cell carcinoma (HNSCC). Therefore, we measured HPRT1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between HPRT1 expression and clinical pathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC), a common type of HNSCC. We built OSCC cells with stable knockdown and overexpression of HPRT1 to observe its influence on chemoresistance and malignancy in vitro and vivo. We found that highly expressed HPRT1 was associated with a poor prognosis and could promote resistance to cisplatin (CDDP) in OSCC cells in both in vitro and in vivo. An RNA sequence assay was carried out to explore the mechanism of function of HPRT1, we found that HPRT1 could positively regulate the expression of MMP1 and the activation of the PI3K/AKT pathway, to regulate the resistance to CDDP of OSCC. In conclusion, HPRT1 can no longer be simply believed to be a housekeeping gene. HPRT1 overexpression indicates a worse prognosis and can improve CDDP resistance for patients with OSCC by promoting the MMP1/PI3K/Akt axis. HPRT1 may be a potential prognostic biomarker and therapeutic target in OSCC.

Xenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized. Real-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay. Herein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens. These findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.