Cell Death Dis: INPP4B deficiency affects DNA double-stranded fracture repair by undermining the stability of Rad50

Genomic instability is a basic feature of malignant tumors, and many gene mutations and large genome changes, including deletion, translocation, loss of heterogeneity and amplification, are accidental factors of tumor occurrenceTumor inhibitors usually play a role in maintaining the stability of the genomePrevious genetic screenings have found that INPP4B (B-type inositol 4-phosphate 4-phosphoasse) can hydrolysis phosphatidyl inositol 3, 4-diphosphate is a potential tumor suppressor in lung cancer cellsHowever, it is not clear how INPP4B regulates the stability of lung cancer cell genomesin thein the study, researchers used Crispr-Cas9 gene editing to knock out the INPP4B gene in lung adenocarcinoma A549 cells, eventually leading to cells' sensitivity to ionizing radiation (IR), PARP inhibitors olaparib, and DNA homologous recombinationReintroduction of the anti-Crispr-Cas9 INPP4B gene in INPP4B knock-out cells can partially restore its resistance to IR, indicating that the absence of INPP4B protein is closely related to the increased sensitivity of cells to IRin addition, researchers found that in A549 cells, ectopically expressed INPP4B responded to IR radiation by redistribution from cytoplasm to the nucleus and by the interaction between endogenous INPP4B protein and Rad50, a key component of the MRN complex associated with double-stranded fracture of DNAThe absence of inEogenous Rad50 stability can lead to a decrease in the tumor suppressor INPP4B, which can play an important role in maintaining genomic integrity by promoting the repair of DNA double-stranded fracture series mediated by Rad50results show that INPP4B can play a dual role in inhibiting tumor development by maintaining genome stability and inhibiting PI3K-Akt-mTOR signal transduction pathway, and provide a personalized new strategy for cancer treatment for patients with clinical lysion of INPP4B deficiency or deficiency