FXR1 regulates transcription and is required for growth of human cancer cells with <i>TP53/FXR2</i> homozygous deletion.

Abstract

Tumor suppressor p53 prevents cell transformation by inducing apoptosis and other responses. Homozygous <i>TP53</i> deletion occurs in various types of human cancers for which no therapeutic strategies have yet been reported. TCGA database analysis shows that the <i>TP53</i> homozygous deletion locus mostly exhibits co-deletion of the neighboring gene <i>FXR2,</i> 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 <i>TP53</i> and <i>FXR2</i> 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 <i>TP53</i> homozygous deletion.