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Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO
Hepatocellular carcinoma (HCC) is one of the most common primary cancers with limited therapeutic options. Melatonin, a neuroendocrine hormone produced primarily by the pineal gland, demonstrates an anti-cancer effect on a myriad of cancers including HCC. However, whether melatonin could suppress tu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9548564/ https://www.ncbi.nlm.nih.gov/pubmed/36225557 http://dx.doi.org/10.3389/fphar.2022.1007006 |
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author | Bai, Lu Sun, Siwen Su, Wenmei Chen, Chaoqun Lv, Yuesheng Zhang, Jinrui Zhao, Jinyao Li, Man Qi, Yangfan Zhang, Wenjing Wang, Yang |
author_facet | Bai, Lu Sun, Siwen Su, Wenmei Chen, Chaoqun Lv, Yuesheng Zhang, Jinrui Zhao, Jinyao Li, Man Qi, Yangfan Zhang, Wenjing Wang, Yang |
author_sort | Bai, Lu |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is one of the most common primary cancers with limited therapeutic options. Melatonin, a neuroendocrine hormone produced primarily by the pineal gland, demonstrates an anti-cancer effect on a myriad of cancers including HCC. However, whether melatonin could suppress tumor growth through regulating RNA alternative splicing remains largely unknown. Here we demonstrated that melatonin could inhibit the growth of HCC. Mechanistically, melatonin induced transcriptional alterations of genes, which are involved in DNA replication, DNA metabolic process, DNA repair, response to wounding, steroid metabolic process, and extracellular matrix functions. Importantly, melatonin controlled numerous cancer-related RNA alternative splicing events, regulating mitotic cell cycle, microtubule-based process, kinase activity, DNA metabolic process, GTPase regulator activity functions. The regulatory effect of melatonin on alternative splicing is partially mediated by melatonin receptor MT1. Specifically, melatonin regulates the splicing of IKBKG (NEMO), an essential modulator of NF-κB. In brief, melatonin increased the production of the long isoform of NEMO-L with exon 5 inclusion, thereby inhibiting the growth of HepG2 cells. Collectively, our study provides a novel mechanism of melatonin in regulating RNA alternative splicing, and offers a new perspective for melatonin in the inhibition of cancer progression. |
format | Online Article Text |
id | pubmed-9548564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95485642022-10-11 Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO Bai, Lu Sun, Siwen Su, Wenmei Chen, Chaoqun Lv, Yuesheng Zhang, Jinrui Zhao, Jinyao Li, Man Qi, Yangfan Zhang, Wenjing Wang, Yang Front Pharmacol Pharmacology Hepatocellular carcinoma (HCC) is one of the most common primary cancers with limited therapeutic options. Melatonin, a neuroendocrine hormone produced primarily by the pineal gland, demonstrates an anti-cancer effect on a myriad of cancers including HCC. However, whether melatonin could suppress tumor growth through regulating RNA alternative splicing remains largely unknown. Here we demonstrated that melatonin could inhibit the growth of HCC. Mechanistically, melatonin induced transcriptional alterations of genes, which are involved in DNA replication, DNA metabolic process, DNA repair, response to wounding, steroid metabolic process, and extracellular matrix functions. Importantly, melatonin controlled numerous cancer-related RNA alternative splicing events, regulating mitotic cell cycle, microtubule-based process, kinase activity, DNA metabolic process, GTPase regulator activity functions. The regulatory effect of melatonin on alternative splicing is partially mediated by melatonin receptor MT1. Specifically, melatonin regulates the splicing of IKBKG (NEMO), an essential modulator of NF-κB. In brief, melatonin increased the production of the long isoform of NEMO-L with exon 5 inclusion, thereby inhibiting the growth of HepG2 cells. Collectively, our study provides a novel mechanism of melatonin in regulating RNA alternative splicing, and offers a new perspective for melatonin in the inhibition of cancer progression. Frontiers Media S.A. 2022-09-26 /pmc/articles/PMC9548564/ /pubmed/36225557 http://dx.doi.org/10.3389/fphar.2022.1007006 Text en Copyright © 2022 Bai, Sun, Su, Chen, Lv, Zhang, Zhao, Li, Qi, Zhang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Bai, Lu Sun, Siwen Su, Wenmei Chen, Chaoqun Lv, Yuesheng Zhang, Jinrui Zhao, Jinyao Li, Man Qi, Yangfan Zhang, Wenjing Wang, Yang Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO |
title | Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO |
title_full | Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO |
title_fullStr | Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO |
title_full_unstemmed | Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO |
title_short | Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO |
title_sort | melatonin inhibits hcc progression through regulating the alternative splicing of nemo |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9548564/ https://www.ncbi.nlm.nih.gov/pubmed/36225557 http://dx.doi.org/10.3389/fphar.2022.1007006 |
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