TY - JOUR TI - FXR1 regulates transcription and is required for growth of human cancer cells with TP53/FXR2 homozygous deletion AU - Fan, Yichao AU - Yue, Jiao AU - Xiao, Mengtao AU - Han-Zhang, Han AU - Wang, Yao Vickie AU - Ma, Chun AU - Deng, Zhilin AU - Li, Yingxiang AU - Yu, Yanyan AU - Wang, Xinghao AU - Niu, Shen AU - Hua, Youjia AU - Weng, Zhiping AU - Atadja, Peter AU - Li, En AU - Xiang, Bin A2 - Davidson, Irwin VL - 6 PY - 2017 DA - 2017/08/02 SP - e26129 C1 - eLife 2017;6:e26129 DO - 10.7554/eLife.26129 UR - https://doi.org/10.7554/eLife.26129 AB - Tumor suppressor p53 prevents cell transformation by inducing apoptosis and other responses. Homozygous TP53 deletion occurs in various types of human cancers for which no therapeutic strategies have yet been reported. TCGA database analysis shows that the TP53 homozygous deletion locus mostly exhibits co-deletion of the neighboring gene FXR2, which belongs to the Fragile X gene family. Here, we demonstrate that inhibition of the remaining family member FXR1 selectively blocks cell proliferation in human cancer cells containing homozygous deletion of both TP53 and FXR2 in a collateral lethality manner. Mechanistically, in addition to its RNA-binding function, FXR1 recruits transcription factor STAT1 or STAT3 to gene promoters at the chromatin interface and regulates transcription thus, at least partially, mediating cell proliferation. Our study anticipates that inhibition of FXR1 is a potential therapeutic approach to targeting human cancers harboring TP53 homozygous deletion. KW - FXR1 KW - p53 deletion KW - collateral lethality KW - fragile X family KW - STAT JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -