A novel lncRNA FUAT1/TNS4 axis confers chemoresistance by suppressing ROS-mediated apoptosis in gastric cancer

Reactive oxygen species (ROS) play a vital role in conveying the cytotoxicity and resistance of most chemo-drugs. Thus, a better understanding of the detailed activities against oxidative stress in cancer cells may provide novel insights into the discovery of common mechanisms underlying chemoresistance. In this study, taking advantage of a customized screening strategy based on transcriptome sequencing (RNA-Seq) technology, we identified a novel lncRNA, designated FUAT1, as a key non-genetic player that participates in ROS-mediated intrinsic chemoresistance in gastric cancer (GC) cells. The role of the FUAT1 regulatory axis in chemoresistance was further explored by using a series of in vitro and in vivo assays, including gain/loss-of-function and rescue experiments. Mechanistically, FUAT1 could upregulate TNS4 by sponging miR-140-5p, allowing GC cells to survive upon chemotherapy via inhibition of ROS-mediated apoptosis. Clinically, the FUAT1/TNS4 regulatory axis is negatively associated with overall and progression-free survival in gastric and colon cancer patients treated with 5-FU adjuvant chemotherapy. Our findings touch on a fundamental adaptive mechanism for the survival of cancer cells upon chemotherapy, providing a novel insight into the development of strategies to overcome chemoresistance. Overall design: To identify the critical player in ROS-mediated chemoresistance,we established untreated(control), 5-FU(7.69uM) and H2O2(80uM)-induced SNU16 cell lines for 24h.We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different treated cells with three replicates.Comparative gene expression profiling analysis of RNA-seq data for control cells and treated cells(5-FU or H2O2).