Selective mechanism of action of dietary peptides from common bean on HCT116 human colorectal cancer cells through loss of mitochondrial membrane potential and DNA damage

2016 ◽  
Vol 23 ◽  
pp. 24-39 ◽  
Author(s):  
Diego A. Luna-Vital ◽  
Elvira González de Mejía ◽  
Guadalupe Loarca-Piña
eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ritu Chaudhary ◽  
Berkley Gryder ◽  
Wendy S Woods ◽  
Murugan Subramanian ◽  
Matthew F Jones ◽  
...  

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.


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