lncRNA‐encoded pep‐AP attenuates the pentose phosphate pathway and sensitizes colorectal cancer cells to Oxaliplatin

  • Wang X
  • Zhang H
  • Yin S
  • et al.
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Abstract

Oxaliplatin (L-OHP) is a standard treatment for colorectal cancer (CRC), but chemoresistance is a considerable challenge. L-OHP shows dose-dependent toxicity, and potential approaches that sensitize cancer cells to L-OHP could reduce the dosage. With the development of translatomics, it was found that some lncRNAs encode short peptides. Here, we use ribosome footprint profiling combined with lncRNA-Seq to screen 12 lncRNAs with coding potential, of which lnc-AP encodes the short peptide pep-AP, for their role in L-OHP resistance. Co-IP and LC-MS/MS data show that the TALDO1 protein interacts with pep-AP and that pep-AP suppresses the expression of TALDO1. The pep-AP/TALDO1 pathway attenuates the pentose phosphate pathway (PPP), reducing NADPH/NADP(+) and glutathione (GSH) levels and causing ROS accumulation and apoptosis, which sensitizes CRC cells to L-OHP in vitro and in vivo. pep-AP thus might become a potential anticancer peptide for future treatments of L-OHP-resistant CRC.

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Wang, X., Zhang, H., Yin, S., Yang, Y., Yang, H., Yang, J., … Ba, Y. (2022). lncRNA‐encoded pep‐AP attenuates the pentose phosphate pathway and sensitizes colorectal cancer cells to Oxaliplatin. EMBO Reports, 23(1). https://doi.org/10.15252/embr.202153140

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