关键词： FXR1 STAT cancer biology collateral lethality fragile X family mouse p53 deletion

Mesh ： Animals Apoptosis / genetics Base Sequence CRISPR-Cas Systems / genetics Cell Line, Tumor Cell Proliferation / genetics Cell Transformation, Neoplastic / genetics Chromatin Female Gene Editing Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Heterografts Homozygote Humans Janus Kinase Inhibitors / analysis Mice Mice, Inbred BALB C Neoplasms / genetics Promoter Regions, Genetic RNA-Binding Proteins / genetics metabolism STAT1 Transcription Factor / genetics STAT3 Transcription Factor / genetics Sequence Deletion Transcription Factors Tumor Suppressor Protein p53 / genetics

来  源：   DOI：10.7554/eLife.26129   PDF(Sci-hub)

Abstract：
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.
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