Open AccessDownregulation of leucine‐rich repeats and immunoglobulin‐like domains 1 by micro RNA ‐20a modulates gastric cancer multidrug resistance
Author(s) -
Zhou Lin,
Li Xiaowei,
Zhou Fan,
Jin Zhi'an,
Chen Di,
Wang Pin,
Zhang Shu,
Zhuge Yuzheng,
Shang Yulong,
Zou Xiaoping
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13538
Subject(s) - downregulation and upregulation , multiple drug resistance , mapk/erk pathway , cancer research , protein kinase b , cancer , biology , untranslated region , microbiology and biotechnology , apoptosis , drug resistance , messenger rna , signal transduction , gene , biochemistry , genetics
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.