Knockdown of NRMT enhances sensitivity of retinoblastoma cells to cisplatin through upregulation of the CENPA/Myc/Bcl2 axis

Chemotherapy resistance of tumor cells causes failure in anti-tumor therapies. Recently, N-terminal regulator of chromatin condensation 1 methyltransferase (NRMT) is abnormally expressed in different cancers. Hence, we speculate that NRMT may pay a crucial role in the development of chemosensitivity...

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Published in:Cell death discovery 2022-01, Vol.8 (1), p.14-14, Article 14
Main Authors: Li, Zhongrui, Zhang, Lan, Liu, Dongrui, Yang, Zhanghui, Xuan, Di, Zhang, Yi
Format: Article
Language:English
Subjects:
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Apoptosis
Bcl-2 protein
Biochemistry
Biomedical and Life Sciences
Cancer
Cell Biology
Cell Cycle Analysis
Cell proliferation
Centromere protein A
Chemoresistance
Chemotherapy
Chromatin
Cisplatin
Experiments
Histones
Immunoprecipitation
Life Sciences
Lysine
Methyltransferase
Myc protein
Retina
Retinoblastoma
Stem Cells
Transcription
Tumor cells
Tumors
Up-regulation
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Summary:Chemotherapy resistance of tumor cells causes failure in anti-tumor therapies. Recently, N-terminal regulator of chromatin condensation 1 methyltransferase (NRMT) is abnormally expressed in different cancers. Hence, we speculate that NRMT may pay a crucial role in the development of chemosensitivity in retinoblastoma. We characterized the upregulation of NRMT in the developed cisplatin (CDDP)-resistant retinoblastoma cell line relative to parental cells. Loss-of-function experiments demonstrated that NRMT silencing enhanced chemosensitivity of retinoblastoma cells to CDDP. Next, NRMT was identified to enrich histone-H3 lysine 4 trimethylation in the promoter of centromere protein A (CENPA) by chromatin immunoprecipitation assay. Rescue experiments suggested that CENPA reduced chemosensitivity by increasing the viability and proliferation and reducing apoptosis of CDDP-resistant retinoblastoma cells, which was reversed by NRMT. Subsequently, CENPA was witnessed to induce the transcription of Myc and to elevate the expression of B cell lymphoma-2. At last, in vivo experiments confirmed the promotive effect of NRMT knockdown on chemosensitivity of retinoblastoma cells to CDDP in tumor-bearing mice. Taken together, NRMT is an inhibitor of chemosensitivity in retinoblastoma. Those findings shed new light on NRMT-targeted therapies for retinoblastoma.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-021-00622-w