BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells

  • Hyunji Choi (Graduate School of New Drug Discovery and Development, Chungnam National University) ;
  • Moonkyung Kang (R&D Center, artiCure Inc.) ;
  • Kee-Ho Lee (Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences) ;
  • Yeon-Soo Kim (Graduate School of New Drug Discovery and Development, Chungnam National University)
  • 투고 : 2023.09.02
  • 심사 : 2023.09.22
  • 발행 : 2023.11.30
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초록

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

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과제정보

This work was supported resources by the artiCure and Chungnam National University.

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