RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways

Ji, Yuan; Shen, Jian; Li, Min; Zhu, Xiaoxiao; Wang, Yanyan; Ding, Jiazheng; Jiang, Shunyao; Chen, Linqi; Wei, Wenxiang

doi:10.7150/ijbs.36829

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Theranostics

International Journal of Medical Sciences

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Journal of Cancer

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Int J Biol Sci 2019; 15(12):2692-2706. doi:10.7150/ijbs.36829 This issue Cite

Research Paper

RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways

Yuan Ji¹, Jian Shen², Min Li³, Xiaoxiao Zhu¹, Yanyan Wang¹, Jiazheng Ding¹, Shunyao Jiang¹, Linqi Chen⁴, Wenxiang Wei^1✉

1. Department of Cell Biology, Institute of Bioengineering, School of Medicine, Soochow University, Suzhou 215123, China
2. Department of Interventional Radiology, First Affiliated Hospital of Soochow University, Suzhou, 215006, China
3. Department of Tumor, People Hospital of Maanshan, Maanshan, 243000, China
4. Department of Endocrinology, Children's Hospital affiliated to Soochow University, Suzhou, 215000, China

Citation:

Ji Y, Shen J, Li M, Zhu X, Wang Y, Ding J, Jiang S, Chen L, Wei W. RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways. Int J Biol Sci 2019; 15(12):2692-2706. doi:10.7150/ijbs.36829. https://www.ijbs.com/v15p2692.htm

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Abstract

The evading apoptosis of tumor cells may result in chemotherapy resistance. Therefore, investigating what molecular events contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity. In this study, we focused on the role of RMP/URI both in cisplatin-induced endogenous apoptosis and in TRAIL-induced exogenous apoptosis in HCC cells. Although flow cytometric analysis indicated that RMP overexpression reduced the apoptosis rate of HCC cells treated with both cisplatin and TRAIL, there was a difference in mechanism between the two treatments. Western blot showed that in intrinsic apoptosis induced by cisplatin, the overexpression of RMP promoted the Bcl-xl expression both in vitro and in vivo. Besides, RMP activated NF-κB/p65(rel) through the phosphorylation of ATM. However, in TRAIL-induced extrinsic apoptosis, RMP significantly suppressed the transcription and expression of P53. Moreover, the forced expression of P53 could offset this inhibitory effect. In conclusion, we presumed that RMP inhibited both intrinsic and extrinsic apoptosis through different signaling pathways. NF-κB was distinctively involved in the RMP circumvention of intrinsic apoptosis, but not in the extrinsic apoptosis of HCC cells. RMP might play an important role in defects of apoptosis, hence the chemotherapeutic resistance in hepatocellular carcinoma. These studies are promising to shed light on a more rational approach to clinical anticancer drug design and therapy.

Keywords: RMP, Apoptosis, ATM, NF-κB, P53

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APA

Ji, Y., Shen, J., Li, M., Zhu, X., Wang, Y., Ding, J., Jiang, S., Chen, L., Wei, W. (2019). RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways. International Journal of Biological Sciences, 15(12), 2692-2706. https://doi.org/10.7150/ijbs.36829.

ACS

Ji, Y.; Shen, J.; Li, M.; Zhu, X.; Wang, Y.; Ding, J.; Jiang, S.; Chen, L.; Wei, W. RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways. Int. J. Biol. Sci. 2019, 15 (12), 2692-2706. DOI: 10.7150/ijbs.36829.

NLM

CSE

Ji Y, Shen J, Li M, Zhu X, Wang Y, Ding J, Jiang S, Chen L, Wei W. 2019. RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways. Int J Biol Sci. 15(12):2692-2706.

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