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Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma

BACKGROUND: RNA binding protein motif (RBM3) is associated with radioresistance in nasopharyngeal carcinoma (NPC), and miR-383-5p was predicted to target the 3'-untranslated region (3'UTR) of RBM3 messenger RNA (mRNA). Our study aimed to investigate the role and the mechanisms of miR-383-5...

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Autores principales: Ma, Rui, Gao, Peng, Yang, Hua, Hu, Jing, Xiao, Jing-Jing, Shi, Mei, Zhao, Li-Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867938/
https://www.ncbi.nlm.nih.gov/pubmed/33569425
http://dx.doi.org/10.21037/atm-20-6881
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author Ma, Rui
Gao, Peng
Yang, Hua
Hu, Jing
Xiao, Jing-Jing
Shi, Mei
Zhao, Li-Na
author_facet Ma, Rui
Gao, Peng
Yang, Hua
Hu, Jing
Xiao, Jing-Jing
Shi, Mei
Zhao, Li-Na
author_sort Ma, Rui
collection PubMed
description BACKGROUND: RNA binding protein motif (RBM3) is associated with radioresistance in nasopharyngeal carcinoma (NPC), and miR-383-5p was predicted to target the 3'-untranslated region (3'UTR) of RBM3 messenger RNA (mRNA). Our study aimed to investigate the role and the mechanisms of miR-383-5p targeting RBM3 in NPC cell proliferation and radioresistance (RR). METHODS: The expression of miR-383-5p was detected by Real-time quantitative PCR (qRT-PCR) between RS (Radiosensitivity) and RR (Radioresistance) NPC patient- tissue specimens and cell lines. Cell Counting Kit-8 (CCK-8) and Clonogenic survival assay were applied to analyze the effect of miR-383-5p on NPC cell proliferation and radioresistance. Possible downstream target of miR-383-5p in NPC cells, RBM3was evaluated by luciferase assay and qRT-PCR. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3 by rescue experiments. The effect of miR-383-5p on radiation-induced apoptosis was explored through Flow cytometric analysis and Western blotting. Western blotting was analyzed the molecular of RBM3-mediated Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) signaling pathways RESULTS: The expression of miR-383-5p was decreased in radioresistant NPC tissues and cells. miR-383-5p inhibited cell proliferation and radioresistance in CNE1/IR cells. We also observed that therapeutic administration of a miR-383-5p agomir dramatically sensitized NPC xenografts to radiation in a mouse model. Conversely, in the same xenograft model, administration of a miR-383-5p antagomir dramatically increased NPC resistance to radiation. miR-383-5p targeted the 3'UTR of RBM3. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3. Finally, we found that miR-383-5p increased radiation-induced apoptosis, activated JNK signaling, and inhibited ERK signaling. CONCLUSIONS: Our study revealed that miR-383-5p targeted the 3'UTR of RBM3 and contributed to the efficacy of NPC radiation therapy by altering the RBM3-mediated JNK and ERK signaling pathways.
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spelling pubmed-78679382021-02-09 Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma Ma, Rui Gao, Peng Yang, Hua Hu, Jing Xiao, Jing-Jing Shi, Mei Zhao, Li-Na Ann Transl Med Original Article BACKGROUND: RNA binding protein motif (RBM3) is associated with radioresistance in nasopharyngeal carcinoma (NPC), and miR-383-5p was predicted to target the 3'-untranslated region (3'UTR) of RBM3 messenger RNA (mRNA). Our study aimed to investigate the role and the mechanisms of miR-383-5p targeting RBM3 in NPC cell proliferation and radioresistance (RR). METHODS: The expression of miR-383-5p was detected by Real-time quantitative PCR (qRT-PCR) between RS (Radiosensitivity) and RR (Radioresistance) NPC patient- tissue specimens and cell lines. Cell Counting Kit-8 (CCK-8) and Clonogenic survival assay were applied to analyze the effect of miR-383-5p on NPC cell proliferation and radioresistance. Possible downstream target of miR-383-5p in NPC cells, RBM3was evaluated by luciferase assay and qRT-PCR. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3 by rescue experiments. The effect of miR-383-5p on radiation-induced apoptosis was explored through Flow cytometric analysis and Western blotting. Western blotting was analyzed the molecular of RBM3-mediated Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) signaling pathways RESULTS: The expression of miR-383-5p was decreased in radioresistant NPC tissues and cells. miR-383-5p inhibited cell proliferation and radioresistance in CNE1/IR cells. We also observed that therapeutic administration of a miR-383-5p agomir dramatically sensitized NPC xenografts to radiation in a mouse model. Conversely, in the same xenograft model, administration of a miR-383-5p antagomir dramatically increased NPC resistance to radiation. miR-383-5p targeted the 3'UTR of RBM3. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3. Finally, we found that miR-383-5p increased radiation-induced apoptosis, activated JNK signaling, and inhibited ERK signaling. CONCLUSIONS: Our study revealed that miR-383-5p targeted the 3'UTR of RBM3 and contributed to the efficacy of NPC radiation therapy by altering the RBM3-mediated JNK and ERK signaling pathways. AME Publishing Company 2021-01 /pmc/articles/PMC7867938/ /pubmed/33569425 http://dx.doi.org/10.21037/atm-20-6881 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Ma, Rui
Gao, Peng
Yang, Hua
Hu, Jing
Xiao, Jing-Jing
Shi, Mei
Zhao, Li-Na
Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma
title Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma
title_full Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma
title_fullStr Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma
title_full_unstemmed Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma
title_short Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma
title_sort inhibition of cell proliferation and radioresistance by mir-383-5p through targeting rna binding protein motif (rbm3) in nasopharyngeal carcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867938/
https://www.ncbi.nlm.nih.gov/pubmed/33569425
http://dx.doi.org/10.21037/atm-20-6881
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