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

  • Original Article – Cancer Research
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Abstract

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.

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Funding

This work was supported by The National Natural Science Foundation of China (Nos. 81760549, 81872480 and 81560492) and Science and Technology Project of Jiangxi Health and Family Planning Commission (No. 20165287).

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Author notes

  1. Lin Xin and Qi Zhou have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    Lin Xin, Qi Zhou, Yi-Wu Yuan, Li-Qiang Zhou, Li Liu, Shi-Hao Li & Chuan liu

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  1. Lin Xin
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  2. Qi Zhou
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  4. Li-Qiang Zhou
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Correspondence to Lin Xin.

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All animal experiments were approved by the Ethics Committee of The Second Affiliated Hospital of Nanchang University, and were conducted in accordance with the Declaration of Helsinki.

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Xin, L., Zhou, Q., Yuan, YW. et al. METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy. J Cancer Res Clin Oncol 145, 2507–2517 (2019). https://doi.org/10.1007/s00432-019-03015-w

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  • DOI: https://doi.org/10.1007/s00432-019-03015-w

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