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bioRxiv · 10.1101/186403

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Zhou, L.·Li, X.·Zhou, F.·Jin, Z.·Chen, D.·Wang, P.·Zhang, S.·Zhuge, Y.·Shang, Y.·Zou, X.
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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 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.

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Zhou, L., Li, X., Zhou, F., Jin, Z., Chen, D., Wang, P., Zhang, S., Zhuge, Y., Shang, Y., Zou, X.. 2017-09-08. Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance. https://doi.org/10.1101/186403

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