@article {Zhou186403, author = {Lin Zhou and Xiaowei Li and Fan Zhou and Zhi{\textquoteright}an Jin and Di Chen and Pin Wang and Shu Zhang and Yuzheng Zhuge and Yulong Shang and Xiaoping Zou}, title = {Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance}, elocation-id = {186403}, year = {2017}, doi = {10.1101/186403}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that up-regulation of LRIG1 enhanced chemo-sensitivity in GC cells. Interestingly, miR-20a, which was overexpressed in GC MDR cell lines and tissues, was identified to regulate LRIG1 expression by directly targeting its 3'untranslated region. We also found that inhibition of miR-20a suppressed GC MDR, and up-regulation showed opposite effects. Moreover, we demonstrated that the miR-20a/LRIG1 axis regulated GC cell MDR through EGFR mediated PI3K/AKT and MAPK/ERK signaling pathways. Finally, LRIG1 expression in human GC tissues is inversely correlated with miR-20a and EGFR. Taken together, the newly identified miR-20a/LRIG1/EGFR link provides insight into the MDR process of GC, and targeting this axis represents a novel potential therapeutic strategy to block GC chemo-resistance.5-FU5-fluorouracilABCB1ATP-binding cassette, sub-family B member 1ABCG2ATP-binding cassette, sub-family G, member2ADRadriamycinAKTprotein kinase BCDDPcisplatinEGFRepidermal growth factor receptorERKextracellular signal-regulated kinaseGAPDHglyceraldehyde 3-phosphate dehydrogenaseGCgastric cancerHER2human epidermal growth factor receptor 2IHCimmunohistochemistryLRIG1leucine-rich repeats and immunoglobulin-like domains 1MAPKmitogen-activated protein kinaseMDRmultidrug resistancemiRmicroRNAmiRNAmicroRNAmRNAmessenger RNAPI3Kphosphatidylinositol 3 kinaseqRT-PCRquantitative reverse transcription{\textendash}polymerase chain reactionsiRNAsilencing RNATNFαtumor necrosis factor αUTRuntranslated regionVCRvincristine}, URL = {https://www.biorxiv.org/content/early/2017/09/08/186403}, eprint = {https://www.biorxiv.org/content/early/2017/09/08/186403.full.pdf}, journal = {bioRxiv} }