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Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression

Hypopharyngeal squamous cell carcinoma (HSCC) is one of the high mortality cancers with a poor prognosis, which is driving the development of new chemotherapeutic agents. We identified the anticancer effects of a natural compound, solamargine (SM), on FaDU cells and explored its mechanism in terms o...

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Autores principales: Meng, Ying, Jin, Mengli, Yuan, Dai, Zhao, Yicheng, Kong, Xiangri, Guo, Xuerui, Wang, Xingye, Hou, Juan, Wang, Bingmei, Song, Wu, Tang, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315292/
https://www.ncbi.nlm.nih.gov/pubmed/35903338
http://dx.doi.org/10.3389/fphar.2022.887387
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author Meng, Ying
Jin, Mengli
Yuan, Dai
Zhao, Yicheng
Kong, Xiangri
Guo, Xuerui
Wang, Xingye
Hou, Juan
Wang, Bingmei
Song, Wu
Tang, Yong
author_facet Meng, Ying
Jin, Mengli
Yuan, Dai
Zhao, Yicheng
Kong, Xiangri
Guo, Xuerui
Wang, Xingye
Hou, Juan
Wang, Bingmei
Song, Wu
Tang, Yong
author_sort Meng, Ying
collection PubMed
description Hypopharyngeal squamous cell carcinoma (HSCC) is one of the high mortality cancers with a poor prognosis, which is driving the development of new chemotherapeutic agents. We identified the anticancer effects of a natural compound, solamargine (SM), on FaDU cells and explored its mechanism in terms of non-coding RNA. It was observed that SM inhibited the proliferation of FaDU cells with an IC(50) of 5.17 μM. High-throughput sequencing data revealed that lncRNA HOXA11-AS was significantly downregulated in cells co-incubated with SM. Further assays demonstrated that SM-induced downregulation of lncRNA HOXA11-AS showed important implications for apoptosis. Given the properties of HOXA11-AS as a miR-155 sponge, we further confirmed that SM upregulated the expression of miR-155 in FaDU cells. C-Myc is a transcription factor that regulates cell differentiation and apoptosis, whose mRNA is considered to be targeted by miR-155. We showed that c-Myc expression was downregulated by SM and accompanied by increased apoptosis, which was consistent with the findings of transcriptome sequencing. Furthermore, SM administration suppressed xenograft tumor growth in a xenograft mouse model in vivo. In the light of the aforementioned findings, our results suggested that SM downregulated the expression of HOXA11-AS, which in turn induces apoptosis by downregulating c-Myc in FaDU, providing evidence for the anticancer effect of SM on HSCC and uncovering the effect of SM on non-coding RNAs as, at least partly, a mechanism of action.
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spelling pubmed-93152922022-07-27 Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression Meng, Ying Jin, Mengli Yuan, Dai Zhao, Yicheng Kong, Xiangri Guo, Xuerui Wang, Xingye Hou, Juan Wang, Bingmei Song, Wu Tang, Yong Front Pharmacol Pharmacology Hypopharyngeal squamous cell carcinoma (HSCC) is one of the high mortality cancers with a poor prognosis, which is driving the development of new chemotherapeutic agents. We identified the anticancer effects of a natural compound, solamargine (SM), on FaDU cells and explored its mechanism in terms of non-coding RNA. It was observed that SM inhibited the proliferation of FaDU cells with an IC(50) of 5.17 μM. High-throughput sequencing data revealed that lncRNA HOXA11-AS was significantly downregulated in cells co-incubated with SM. Further assays demonstrated that SM-induced downregulation of lncRNA HOXA11-AS showed important implications for apoptosis. Given the properties of HOXA11-AS as a miR-155 sponge, we further confirmed that SM upregulated the expression of miR-155 in FaDU cells. C-Myc is a transcription factor that regulates cell differentiation and apoptosis, whose mRNA is considered to be targeted by miR-155. We showed that c-Myc expression was downregulated by SM and accompanied by increased apoptosis, which was consistent with the findings of transcriptome sequencing. Furthermore, SM administration suppressed xenograft tumor growth in a xenograft mouse model in vivo. In the light of the aforementioned findings, our results suggested that SM downregulated the expression of HOXA11-AS, which in turn induces apoptosis by downregulating c-Myc in FaDU, providing evidence for the anticancer effect of SM on HSCC and uncovering the effect of SM on non-coding RNAs as, at least partly, a mechanism of action. Frontiers Media S.A. 2022-07-12 /pmc/articles/PMC9315292/ /pubmed/35903338 http://dx.doi.org/10.3389/fphar.2022.887387 Text en Copyright © 2022 Meng, Jin, Yuan, Zhao, Kong, Guo, Wang, Hou, Wang, Song and Tang. 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
Meng, Ying
Jin, Mengli
Yuan, Dai
Zhao, Yicheng
Kong, Xiangri
Guo, Xuerui
Wang, Xingye
Hou, Juan
Wang, Bingmei
Song, Wu
Tang, Yong
Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression
title Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression
title_full Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression
title_fullStr Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression
title_full_unstemmed Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression
title_short Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression
title_sort solamargine inhibits the development of hypopharyngeal squamous cell carcinoma by decreasing lncrna hoxa11-as expression
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315292/
https://www.ncbi.nlm.nih.gov/pubmed/35903338
http://dx.doi.org/10.3389/fphar.2022.887387
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