Fig. 8. A schematic diagram of miR-301a-3p based signalling circuit of trastuzumab resistance in HER2-positive GC.

miR-301a-3p promoted trastuzumab resistance in ER stressed GC cells by downregulating the expression of LRIG1, resulting in an increase in the expression of IGF-1R and FGFR1, and the activation of ERK and AKT signalling pathway. Moreover, miR-301a-3p could be carried by exosomes and secreted by ER stressed GC cells, transmitting trastuzumab resistance to unstressed recipient cells.