2. Academic Validation
  3. De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma

De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma

  • Sci Rep. 2021 Jun 29;11(1):13474. doi: 10.1038/s41598-021-92948-9.
Ami Maruyama 1 2 3,  Yuzo Sato 1 2 4 5,  Joji Nakayama 1 2 3,  Junko Murai 4 5,  Takamasa Ishikawa 5 6,  Tomoyoshi Soga 4 5,  Hideki Makinoshima 7 8 9 10
Affiliations

Affiliations

  • 1 Shonai Regional Industry Promotion Center, Tsuruoka, Yamagata, 997-0052, Japan.
  • 2 Tsuruoka Metabolomics Laboratory, National Cancer Center, Mizukami 246-2, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan.
  • 3 Division of Translational Research, Exploratory Oncology Research, and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan.
  • 4 Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, 252-0882, Japan.
  • 5 Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0035, Japan.
  • 6 Infinity Lab Inc., Mizukami 246-2, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan.
  • 7 Shonai Regional Industry Promotion Center, Tsuruoka, Yamagata, 997-0052, Japan. hmakinos@east.ncc.go.jp.
  • 8 Tsuruoka Metabolomics Laboratory, National Cancer Center, Mizukami 246-2, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan. hmakinos@east.ncc.go.jp.
  • 9 Division of Translational Research, Exploratory Oncology Research, and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan. hmakinos@east.ncc.go.jp.
  • 10 Faculty of Medicine, Yamagata University, Yamagata, 990-9585, Japan. hmakinos@east.ncc.go.jp.
PMID: 34188151 DOI: 10.1038/s41598-021-92948-9
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.

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