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Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named  PINCR  (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC)  in vitro  and tumor growth  in vivo . Targeted deletion of  PINCR  in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs.  PINCR  regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including  BTG2, RRM2B  and  GPX1 . Using a novel RNA pulldown approach that utilized endogenous S1-tagged  PINCR , we show that  PINCR  associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/ PINCR /Matrin 3 axis in response to DNA damage in CRC cells.

Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3