Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells
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Pleiotropic regulator 1 (PLRG1), a highly conserved element inthe spliceosome, can form a NineTeen Complex (NTC) withPrp19, SPF27, and CDC5L. This complex plays crucial roles inboth pre-mRNA splicing and DNA repair processes. Here, weprovide evidence that PLRG1 has a multifaceted impact oncancer cell proliferation. Comparing its expression levels incancer and normal cells, we observed that PLRG1 was upregulatedin various tumor tissues and cell lines. Knockdown ofPLRG1 resulted in tumor-specific cell death. Depletion of PLRG1had notable effects, including mitotic arrest, microtubule instability,endoplasmic reticulum (ER) stress, and accumulation ofautophagy, ultimately culminating in apoptosis. Our results alsodemonstrated that PLRG1 downregulation contributed to DNAdamage in cancer cells, which we confirmed through experimentalvalidation as DNA repair impairment. Interestingly, whenPLRG1 was decreased in normal cells, it induced G1 arrest asa self-protective mechanism, distinguishing it from effects observedin cancer cells. These results highlight multifaceted impactsof PLRG1 in cancer and underscore its potential as a novelanti-cancer strategy by selectively targeting cancer cells.
Abstract
Pleiotropic regulator 1 (PLRG1), a highly conserved element inthe spliceosome, can form a NineTeen Complex (NTC) withPrp19, SPF27, and CDC5L. This complex plays crucial roles inboth pre-mRNA splicing and DNA repair processes. Here, weprovide evidence that PLRG1 has a multifaceted impact oncancer cell proliferation. Comparing its expression levels incancer and normal cells, we observed that PLRG1 was upregulatedin various tumor tissues and cell lines. Knockdown ofPLRG1 resulted in tumor-specific cell death. Depletion of PLRG1had notable effects, including mitotic arrest, microtubule instability,endoplasmic reticulum (ER) stress, and accumulation ofautophagy, ultimately culminating in apoptosis. Our results alsodemonstrated that PLRG1 downregulation contributed to DNAdamage in cancer cells, which we confirmed through experimentalvalidation as DNA repair impairment. Interestingly, whenPLRG1 was decreased in normal cells, it induced G1 arrest asa self-protective mechanism, distinguishing it from effects observedin cancer cells. These results highlight multifaceted impactsof PLRG1 in cancer and underscore its potential as a novelanti-cancer strategy by selectively targeting cancer cells.
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