Abstract
Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene; however, recent reports suggest that it is upregulated in several cancers and is associated with clinical outcomes. HPRT1 is located on chromosome X and encodes the HPRT enzyme, which functions in recycling nucleotides to supply for DNA and RNA synthesis in actively dividing cells. Here, we used transcriptomic analyses to interrogate its expression across all known cancer types and elucidated its role in regulating gene expression in breast cancer. We observed elevated HPRT1 RNA levels in malignant tissues when compared to normal controls, indicating its potential as a diagnostic and prognostic marker. Further, in breast cancer, the subtype-specific analysis showed that its expression was highest in basal and triple-negative breast cancer, and HPRT1 knockdown in breast cancer cells suggested that HPRT1 positively regulates genes related to cancer pathways. Collectively, our results essentially highlight the importance of and change the way in which HPRT1’s function is studied in biology, warranting careful examination of its role in cancer.
Highlights
Hypoxanthine phosphoribosyl transferase 1 (HPRT1) codes for the HPRT enzyme, a protein essential in providing the necessary building blocks for future cell growth
Our results revealed that HPRT1 expression is elevated in a majority of the cancers, including breast cancer, and is a critical regulator of cellular pathways associated with rapid cell growth in basal subtype breast tumors
The expression of HPRT1 was elevated when aggregated across cancer types in comparison to its expression aggregated across normal tissues (Figure 1A)
Summary
Hypoxanthine phosphoribosyl transferase 1 (HPRT1) codes for the HPRT enzyme, a protein essential in providing the necessary building blocks for future cell growth. Cancers 2020, 12, 1522 levels varied widely in a large cohort of both normal and malignant samples of different tissue origin, with breast cancer exhibiting the highest average HPRT1 compared to other malignancies [4]. Studies from various cancers, such as colorectal cancer, have shown elevated levels of HPRT1 in tumor samples compared to normal tissues [3,4,5]. The same study found HPRT1 localizes to the surface of the cell membrane in more progressive types of colorectal cancer [4,5]. Prostate cancer patient samples showed an increased expression of HPRT1 when compared to normal tissues [3]
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