scholarly journals Hypoxanthine Phosphoribosyl Transferase 1 Is Upregulated, Predicts Clinical Outcome and Controls Gene Expression in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1522
Author(s):  
Melina J. Sedano ◽  
Enrique I. Ramos ◽  
Ramesh Choudhari ◽  
Alana L. Harrison ◽  
Ramadevi Subramani ◽  
...  

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.

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1204
Author(s):  
Moumita Chakraborty ◽  
Michal Hershfinkel

Zinc (Zn2+) plays an essential role in epithelial physiology. Among its many effects, most prominent is its action to accelerate cell proliferation, thereby modulating wound healing. It also mediates affects in the gastrointestinal system, in the testes, and in secretory organs, including the pancreas, salivary, and prostate glands. On the cellular level, Zn2+ is involved in protein folding, DNA, and RNA synthesis, and in the function of numerous enzymes. In the mammary gland, Zn2+ accumulation in maternal milk is essential for supporting infant growth during the neonatal period. Importantly, Zn2+ signaling also has direct roles in controlling mammary gland development or, alternatively, involution. During breast cancer progression, accumulation or redistribution of Zn2+ occurs in the mammary gland, with aberrant Zn2+ signaling observed in the malignant cells. Here, we review the current understanding of the role of in Zn2+ the mammary gland, and the proteins controlling cellular Zn2+ homeostasis and signaling, including Zn2+ transporters and the Gq-coupled Zn2+ sensing receptor, ZnR/GPR39. Significant advances in our understanding of Zn2+ signaling in the normal mammary gland as well as in the context of breast cancer provides new avenues for identification of specific targets for breast cancer therapy.


2018 ◽  
Vol 50 (12) ◽  
pp. 1015-1025 ◽  
Author(s):  
Jinyi Xing ◽  
Wenqian Jing ◽  
Yujie Zhang ◽  
Lin Liu ◽  
Junjie Xu ◽  
...  

Folate plays an important role in DNA and RNA synthesis by donating methyl groups. To investigate the effects of maternal folate deficiency (FD) on the abdominal adipose transcriptome and on the accumulation of lipid droplets in the liver tissue of chicken offspring, differentially expressed genes (DEGs) of FD were identified with digital gene expression tag profiling. Ultramicroscopy suggested that the size of lipid droplets in hepatocytes increased with FD, while the lipid droplets population number was largely not affected. The serum parameters assay showed that the concentrations of MTHFR (476.57 vs. 395.27), DHFR (45.056 vs. 38.952), LPL (50.408 vs. 48.677), HCY (4.354 vs. 3.836), LEP (9.951 vs. 8.673), and IGF2 (1209.4 vs. 1027.7) in offspring serum of the FD group were significantly higher than those of the normal folate (NF) group ( P < 0.01). The 442 DEGs between NF and FD groups were identified by digital gene expression profiling. Considering the DEGs in the FD groups vs. NF groups, 179 genes were upregulated while 263 downregulated, and in particular, 145 upregulated and 214 downregulated DEGs were successfully annotated with the nonredundant database. Gene Ontology analysis showed that FD mainly affected cellular processes, cell part and binding, cell killing, virions, and receptor regulator activity. With pathway analysis, it indicated that 123 unigenes were assigned to 115 KEGG pathways, but only five of 115 these pathways were significantly enriched with P values ≤ 0.05. Taken together, these results provide a foundation for further studying the responses of offspring to maternal FD in breeding chickens.


Weed Science ◽  
1976 ◽  
Vol 24 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Thomas L. Rost ◽  
David E. Bayer

Propham (Isopropyl carbanilate) at 10-5M concentration does not inhibit DNA synthesis nor does it reduce the number of dividing cells. It does, however, induce a number of abnormal mitotic figures. At higher concentrations (10-3M) propham inhibits DNA, RNA, and protein synthesis as well as stopping entry of cells into mitosis and causing those which divide to be aberrant. DNA and RNA synthesis are not inhibited for approximately 3 hr, while protein synthesis is reduced within 1 hr. The metabolic inhibitory effect of propham is reversible at least in roots treated for 8 hr. The most likely mode of action of propham is the inhibition of certain mitotic specific proteins, or possibly some kind of protein binding function as has been suggested in the literature.


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