Project description:To screen the microRNA regulated by Twist1 and Bmi1 Establish stable transfectants of pSUPER-sh-Twist1 or pSUPER-sh-Bmi1 in OECM1 cells and analyze the miRNA expression level of by microRNA microarray. OECM1 transfected with pSUPER-sh-scr was used as a control experiment.
Project description:We report the expression anaysis of neural stem cells lacking p53, ATMIN, or both. p53-deficent cells form GBM, which is significanly delayed in the absence of ATMIN.
Project description:Despite the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved the patients' survival and became the standard of care for advanced nasopharyngeal carcinoma (NPC), some patients could not benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, we identified ATMIN as a chemoresistance gene in response to TPF therapy in NPC patients. We found that USP10 deubiquitinates and stabilizes ATMIN protein. Knockdown of ATMIN inhibits the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells in vitro and in vivo. Mechanistically, RNA-seq combined with ChIP-seq analysis suggests that ATMIN is associated with the cell death signaling. ATMIN transcriptionally activates LCK to facilitate cell proliferation and docetaxel-resistance. Our findings broaden the insight into the mechanism of chemoresistance in NPC and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
Project description:Despite the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved the patients' survival and became the standard of care for advanced nasopharyngeal carcinoma (NPC), some patients could not benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, we identified ATMIN as a chemoresistance gene in response to TPF therapy in NPC patients. We found that USP10 deubiquitinates and stabilizes ATMIN protein. Knockdown of ATMIN inhibits the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells in vitro and in vivo. Mechanistically, RNA-seq combined with ChIP-seq analysis suggests that ATMIN is associated with the cell death signaling. ATMIN transcriptionally activates LCK to facilitate cell proliferation and docetaxel-resistance. Our findings broaden the insight into the mechanism of chemoresistance in NPC and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
Project description:The cellular response to replication stress requires the DNA-damage responsive kinase ATM and its co-factor ATMIN, however the roles of this signaling pathway following replication stress are unclear. RNA-seq and subsequent differential expression analyses were utilized to identify the functions of ATM and ATMIN in response to replication stress induced by Aphidcolin (APH). Mouse Embryonic Fibroblasts (MEFs) deleted for ATM or ATMIN were treated with 1µM APH or DMSO as a control. Two different wild-type MEF cell lines (wtATM, wtATMIN) served as controls. RNA-seq was performed in duplicates, in a total of 32 samples, with an average of 31.1M aligned readsobtained per group,with 15.5M reads obtained per replicate.
Project description:The cellular response to replication stress requires the DNA-damage responsive kinase ATM and its co-factor ATMIN, however the roles of this signaling pathway following replication stress are unclear. RNA-seq and subsequent differential expression analyses were utilized to identify the functions of ATM and ATMIN in response to replication stress induced by Aphidcolin (APH).