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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 ( LRIG 1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that  LRIG 1 was overexpressed in chemosensitive  GC  tissues and decreased expression of  LRIG 1 predicted poor survival in  GC  patients. We observed that upregulation of  LRIG 1 enhanced chemosensitivity in  GC  cells. Interestingly, miR‐20a, which was overexpressed in  GC MDR  cell lines and tissues, was identified to regulate  LRIG 1 expression by directly targeting its 3′ untranslated region. We also found that inhibition of miR‐20a suppressed  GC MDR , and upregulation showed opposite effects. Moreover, we demonstrated that the miR‐20a/ LRIG 1 axis regulated  GC  cell  MDR  through epidermal growth factor receptor ( EGFR )‐mediated  PI 3K/ AKT  and  MAPK / ERK  signaling pathways. Finally,  LRIG 1 expression in human  GC  tissues is inversely correlated with miR‐20a and  EGFR . Taken together, the newly identified miR‐20a/ LRIG 1/ EGFR  link provides insight into the  MDR  process of  GC , and targeting this axis represents a novel potential therapeutic strategy to block  GC  chemoresistance.

Downregulation of leucine‐rich repeats and immunoglobulin‐like domains 1 by micro RNA ‐20a modulates gastric cancer multidrug resistance