biostudies-literatureTatsumi Athe Japan Society for the Promotion of Science and Kawano Masanori Memorial Foundation for Promotion of Pediatrics1551https://www.ebi.ac.uk/biostudies/studies/S-EPMC9687188biostudies-literatureUnknown11(11)Mutations in <i>NRAS</i> constitutively activate cell proliferation signaling in malignant neoplasms, such as leukemia and melanoma, and the clarification of comprehensive downstream genes of <i>NRAS</i> might lead to the control of cell-proliferative signals of <i>NRAS</i>-driven cancers. We previously established that <i>NRAS</i> expression and proliferative activity can be controlled with doxycycline and named as THP-1 B11. Using a CRISPR activation library on THP-1 B11 cells with the <i>NRAS</i>-off state, survival clones were harvested, and 21 candidate genes were identified. By inducting each candidate guide RNA with the CRISPR activation system, <i>DOHH</i>, <i>HIST1H2AC</i>, <i>KRT32</i>, and <i>TAF6</i> showed higher cell-proliferative activity. The expression of <i>DOHH</i>, <i>HBiologyIdentification of <i>NRAS</i> Downstream Genes with CRISPR Activation Screening.PMC968718818K06953Yamamoto KInoue SFuruno HTaguchi TOnishi ILargaespada DAKitagawa MTanaka YSachs ZKurata MIkeda MIshibashi STatsumi AHirakochi HfalseIdentification of <i>NRAS</i> Downstream Genes with CRISPR Activation Screening.Mutations in <i>NRAS</i> constitutively activate cell proliferation signaling in malignant neoplasms, such as leukemia and melanoma, and the clarification of comprehensive downstream genes of <i>NRAS</i> might lead to the control of cell-proliferative signals of <i>NRAS</i>-driven cancers. We previously established that <i>NRAS</i> expression and proliferative activity can be controlled with doxycycline and named as THP-1 B11. Using a CRISPR activation library on THP-1 B11 cells with the <i>NRAS</i>-off state, survival clones were harvested, and 21 candidate genes were identified. By inducting each candidate guide RNA with the CRISPR activation system, <i>DOHH</i>, <i>HIST1H2AC</i>, <i>KRT32</i>, and <i>TAF6</i> showed higher cell-proliferative activity. The expression of <i>DOHH</i>, <i>H2022-01-01T00:00:00Z2022 Oct2025-04-18T14:59:39.742Z2025-04-07T01:24:30.629ZS-EPMC96871883635825410.3390/biology11111551