lncRNA-encoded pep-AP attenuates the pentose phosphate pathway and sensitizes colorectal cancer cells to Oxaliplatin.
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.
['Wang|Xinyi|X|https://orcid.org/0000-0003-4255-6595', 'Zhang|Haiyang|H|', 'Yin|Shengjie|S|', 'Yang|Yuchong|Y|', 'Yang|Haiou|H|', 'Yang|Jiayu|J|', 'Zhou|Zhengyang|Z|', 'Li|Shuang|S|', 'Ying|Guoguang|G|https://orcid.org/0000-0002-7264-1224', 'Ba|Yi|Y|https://orcid.org/0000-0003-0255-4376']
pentose phosphate pathway lncRNA peptide ROS oxaliplatin resistance