Chemotherapy is currently the main treatment for unresectable or advanced postoperative
gastric cancers. However, its efficacy is negatively affected by the occurrence of chemoresistance, which severely affects patient prognosis. Recently, dysregulation in autophagy has been suggested as a potential mechanism for chemoresistence, and
long noncoding RNA (
lncRNA) also shows its regulatory role in
cancer drug resistance. Using
RNA sequencing, we found that
lncRNA EIF3J-DT was highly expressed in drug-resistant
gastric cancer cells. In-vitro and in-vivo experiments showed that EIF3J-DT activated autophagy and induced drug resistance in
gastric cancer cells by targeting ATG14. Bioinformatics and experimental results showed that EIF3J-DT regulated the expression of ATG14 through direct binding to enhance stabilization of ATG14
mRNA and via blocking the degradation of ATG14
mRNA through competitively binding with
microRNA (
miRNA) MIR188-3p. Therefore, EIF3J-DT increased the expression of ATG14, contributing to activation of autophagy and chemoresistance. Furthermore, it was confirmed that EIF3J-DT and ATG14 were highly expressed in
gastric cancer patients resistant to
chemotherapy, and this was closely associated with patient prognosis. In conclusion, EIF3J-DT is involved in the regulation of autophagy and chemoresistance in
gastric cancer cells by targeting ATG14. It may be a suitable new target for enhancing chemosensitivity and improving prognosis.Abbreviations: 3-MA: 3-methyladenine; 5-Fu:
5-fluorouracil; ATG: autophagy related; C-
CASP3: cleaved
caspase 3; C-CASP7: cleaved
caspase 7; C-PARP: cleaved PARP; CQ:
chloroquine; CR: complete response; DIG:
digoxigenin; ESR1:
estrogen receptor 1; FBS:
fetal bovine serum; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; ISH: in situ hybridization;
lncRNA:
long noncoding RNA;
miRNA:
microRNA; MUT: mutant; NC: negative control; OXA:
oxaliplatin; PBS:
phosphate-buffered saline; PD: progressive disease; PFA:
paraformaldehyde; PR: partial response; qPCR: quantitative polymerase chain reaction; RAPA:
rapamycin; SD: stable disease; TEM: transmission electron microscopy; WT: wild type.