Downregulation of leucine‐rich repeats and immunoglobulin‐like domains 1 by microRNA‐20a modulates gastric cancer multidrug resistance |
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| Authors: | Lin Zhou Xiaowei Li Fan Zhou Zhi'an Jin Di Chen Pin Wang Shu Zhang Yuzheng Zhuge Yulong Shang Xiaoping Zou |
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| Affiliation: | 1. Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China;2. Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China;3. State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China;4. The Second Outpatient Department of Chengdu Army Region Authority, Chengdu, China |
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| 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 chemosensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that upregulation of LRIG1 enhanced chemosensitivity 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 upregulation showed opposite effects. Moreover, we demonstrated that the miR‐20a/LRIG1 axis regulated GC cell MDR through epidermal growth factor receptor (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 chemoresistance. |
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| Keywords: | epidermal growth factor receptor gastric cancer leucine‐rich repeats and immunoglobulin‐like domains 1 miR‐20a multidrug resistance |
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