miR-181a-3p in Exosomes Regulates Lung Cancer Resistance to Amilorotinib Through the UPR/ERAD Pathway Axis
Objective To investigate that miR-181a-3p in exosomes regulates lung cancer resistance to amiloride through the unfolded protein response(UPR)/endoplasmic reticulum-associated protein degradation(ERAD)pathway axis.Meth-ods Human non-small cell lung cancer cells HCC827 were selected for culture and transfected with HCC827 cells(HCC827/Anl cells)induced to be resistant to amilorotinib by continuous treatment using graded concentrations of amilorotinib,and divided into a blank group,a control group,and a miR-181a-3p inhibitor group.qRT-PCR was performed to detect the miR-181a-3p expres-sion.qRT-PCR was performed to detect the activity of HCC827/Anl cells.Flow cytometry was used to detect apoptosis of HCC827/Anl cells.transwell assay was used to detect migration and invasion of HCC827/Anl cells.western blot was used to de-tect the expression of UPR/ERAD pathway related proteins.Dual luciferase reporter detected miR-181a-3p,eIF2α,HRD1 rela-tionship.Results There was no difference in cell proliferation rate,invasion and migrated cell number between blank group and control group(P＞0.05).miR-181a-3p inhibitor group had significantly lower cell proliferation rate,invasion and migrated cell number compared with blank group and control group(P＜0.05).There was no significant difference in eIF2α-MUT and HRD1-MUT between the control group and miR-181a-3p inhibitor group(P＞0.05);compared with the control group,eIF2α-WT and HRD1-WT were significantly lower in miR-181a-3p inhibitor group(P＜0.05).Conclusion miR-181a-3p expression is signifi-cantly up-regulated in lung cancer amilorotinib-resistant cells,whereas miR-181a-3p may regulate the proliferation,invasion and migration of lung cancer drug-resistant cells through exosome encapsulation transporter-activated UPR/ERAD pathway axis,which enhances the drug-resistant of lung cancer to amilorotinib.
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