De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma
Abstract Deoxyribonucleotide biosynthesis from ribonucleotides supports the growth of active cancer cells by producing building blocks for DNA. Although ribonucleotide reductase (RNR) is known to catalyze the rate-limiting step of de novo deoxyribonucleotide triphosphate (dNTP) synthesis, the biolog...
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Nature Portfolio
2021
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oai:doaj.org-article:e15465d288934f60aca475f9ca9bc8022021-12-02T18:18:51ZDe novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma10.1038/s41598-021-92948-92045-2322https://doaj.org/article/e15465d288934f60aca475f9ca9bc8022021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92948-9https://doaj.org/toc/2045-2322Abstract Deoxyribonucleotide biosynthesis from ribonucleotides supports the growth of active cancer cells by producing building blocks for DNA. Although ribonucleotide reductase (RNR) is known to catalyze the rate-limiting step of de novo deoxyribonucleotide triphosphate (dNTP) synthesis, the biological function of the RNR large subunit (RRM1) in small-cell lung carcinoma (SCLC) remains unclear. In this study, we established siRNA-transfected SCLC cell lines to investigate the anticancer effect of silencing RRM1 gene expression. We found that RRM1 is required for the full growth of SCLC cells both in vitro and in vivo. In particular, the deletion of RRM1 induced a DNA damage response in SCLC cells and decreased the number of cells with S phase cell cycle arrest. We also elucidated the overall changes in the metabolic profile of SCLC cells caused by RRM1 deletion. Together, our findings reveal a relationship between the deoxyribonucleotide biosynthesis axis and key metabolic changes in SCLC, which may indicate a possible link between tumor growth and the regulation of deoxyribonucleotide metabolism in SCLC.Ami MaruyamaYuzo SatoJoji NakayamaJunko MuraiTakamasa IshikawaTomoyoshi SogaHideki MakinoshimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
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Medicine R Science Q Ami Maruyama Yuzo Sato Joji Nakayama Junko Murai Takamasa Ishikawa Tomoyoshi Soga Hideki Makinoshima De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma |
| description |
Abstract Deoxyribonucleotide biosynthesis from ribonucleotides supports the growth of active cancer cells by producing building blocks for DNA. Although ribonucleotide reductase (RNR) is known to catalyze the rate-limiting step of de novo deoxyribonucleotide triphosphate (dNTP) synthesis, the biological function of the RNR large subunit (RRM1) in small-cell lung carcinoma (SCLC) remains unclear. In this study, we established siRNA-transfected SCLC cell lines to investigate the anticancer effect of silencing RRM1 gene expression. We found that RRM1 is required for the full growth of SCLC cells both in vitro and in vivo. In particular, the deletion of RRM1 induced a DNA damage response in SCLC cells and decreased the number of cells with S phase cell cycle arrest. We also elucidated the overall changes in the metabolic profile of SCLC cells caused by RRM1 deletion. Together, our findings reveal a relationship between the deoxyribonucleotide biosynthesis axis and key metabolic changes in SCLC, which may indicate a possible link between tumor growth and the regulation of deoxyribonucleotide metabolism in SCLC. |
| format |
article |
| author |
Ami Maruyama Yuzo Sato Joji Nakayama Junko Murai Takamasa Ishikawa Tomoyoshi Soga Hideki Makinoshima |
| author_facet |
Ami Maruyama Yuzo Sato Joji Nakayama Junko Murai Takamasa Ishikawa Tomoyoshi Soga Hideki Makinoshima |
| author_sort |
Ami Maruyama |
| title |
De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma |
| title_short |
De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma |
| title_full |
De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma |
| title_fullStr |
De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma |
| title_full_unstemmed |
De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma |
| title_sort |
de novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/e15465d288934f60aca475f9ca9bc802 |
| work_keys_str_mv |
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| _version_ |
1718378187259379712 |