METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy

Background Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of autophagy and CDDP resistance of gastric cancer cells is still not clear. Materials and methods Western blot...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2019-10, Vol.145 (10), p.2507-2517
Main Authors: Xin, Lin, Zhou, Qi, Yuan, Yi-Wu, Zhou, Li-Qiang, Liu, Li, Li, Shi-Hao, liu, Chuan
Format: Article
Language:English
Subjects:
Autophagy
Cancer Research
Cell viability
Chemotherapy
Cholecystokinin
Cisplatin
Drug resistance
Gastric cancer
Hematology
Internal Medicine
MDR1 protein
Medicine
Medicine & Public Health
Multidrug resistance
Oncology
Original Article – Cancer Research
P-Glycoprotein
Phagocytosis
Ribonucleic acid
RNA
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Summary:Background Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of autophagy and CDDP resistance of gastric cancer cells is still not clear. Materials and methods Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay. Results Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo. Conclusion METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-019-03015-w