Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells

Pleiotropic Regulator 1 (PLRG1), a highly conserved element in the spliceosome, associates with Prp19, SPF27, and CDC5L to form a Ninety complex (NTC). 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 in cancer and normal, we observed that PLRG1 is upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 leads to notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our findings also demonstrate that PLRG1 downregulation contributes to DNA damage in cancer cells, which we confirm through experimental validation as impairing DNA repair. Interestingly, when PLRG1 is decreased in normal cells, it induces G1 arrest as a self-protective mechanism, distinguishing it from the effects observed in cancer cells. These results highlight the multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.