Abstract
Simple SummaryHypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene, however, 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. Hence, HPRT1 can no longer be simply believed to be a housekeeping gene. HPRT1 over- expression indicates a worse prognosis and can improve CDDP resistance for patients with OSCC by promoting the MMP1/PI3K/Akt axis, and it may be a potential prognostic biomarker and thera- peutic target in OSCC.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.
Highlights
Oral squamous cell carcinoma (OSCC) is a common type of head and neck squamous cell carcinoma (HNSCC), which ranked as the sixth most common malignant tumor around the world with a poor prognosis, a high incidence rate, and a mortality rate [1]
Kaplan-Meier survival curves showed that patients with high expression of Hypoxanthine phosphoribosyl transferase 1 (HPRT1) had worse overall survival (OS) and disease-free survival (DFS) compared to those patients with low expression of HPRT1 (Figure 1C), indicating that HPRT1 is a potential prognostic index in HNSCC
We found that highly expressed HPRT1 was associated with poor prognosis and the OS of kidney renal papillary cell carcinoma (KIRP) (p = 0.00026), brain lower grade glioma (LGG) (p = 0.031), liver hepatocellular carcinoma (LIHC) (p = 0.017), uterine carcinosarcoma (UCS) (p = 0.0091), lung adenocarcinoma (LUAD) (p = 0.023), lung squamous cell carcinoma (LUSC) (p = 0.023), mesothelioma (MESO) (p = 3.3 × 10−6) within the The Cancer Genome Atlas (TCGA) project (Figure 7B)
Summary
Oral squamous cell carcinoma (OSCC) is a common type of head and neck squamous cell carcinoma (HNSCC), which ranked as the sixth most common malignant tumor around the world with a poor prognosis, a high incidence rate, and a mortality rate [1]. The high rate of recurrence and distant metastasis results in cancer-related deaths and a five-year survival rate of OSCC of less than 50%. Despite the evolving development of treatment technology, cisplatin (CDDP) remains the first-line treatment regimen in patients with OSCC with recurrence and progression [2,3]. CDDP resistance is a huge obstacle to the efficacy of OSCC treatment, and can lead to early recurrence and metastasis. Biomarkers of resistance to CDDP are rare. It is significant to explore the molecular mechanism of CDDP resistance, to identify effective predictors
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