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RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation

Lung cancer is the leading cause of cancer death worldwide, and the overall survival rate of advanced lung cancer patients is unsatisfactory. Ribosomal proteins (RPs) play important roles in carcinogenesis. However, the role of RPL32 in lung cancer has not been demonstrated. Here, we report that RPL...

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Detalles Bibliográficos
Autores principales: Xie, Jiansheng, Zhang, Wei, Liang, Xiaojing, Shuai, Chong, Zhou, Yubin, Pan, Hongming, Yang, Yunhai, Han, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281510/
https://www.ncbi.nlm.nih.gov/pubmed/32516735
http://dx.doi.org/10.1016/j.omtn.2020.05.019
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author Xie, Jiansheng
Zhang, Wei
Liang, Xiaojing
Shuai, Chong
Zhou, Yubin
Pan, Hongming
Yang, Yunhai
Han, Weidong
author_facet Xie, Jiansheng
Zhang, Wei
Liang, Xiaojing
Shuai, Chong
Zhou, Yubin
Pan, Hongming
Yang, Yunhai
Han, Weidong
author_sort Xie, Jiansheng
collection PubMed
description Lung cancer is the leading cause of cancer death worldwide, and the overall survival rate of advanced lung cancer patients is unsatisfactory. Ribosomal proteins (RPs) play important roles in carcinogenesis. However, the role of RPL32 in lung cancer has not been demonstrated. Here, we report that RPL32 is aberrantly, highly expressed in lung cancer tissues and that the overexpression of RPL32 is correlated with the poor prognosis of these patients. RPL32 silencing significantly inhibited the proliferation of lung cancer cells, with an observed p53 accumulation and cell-cycle arrest. Mechanistically, knockdown of RPL32 resulted in ribosomal stress and affected rRNA maturation. RPL5 and RPL11 sensed stress and translocated from the nucleus to the nucleoplasm, where they bound to murine double minute 2 (MDM2), an important p53 E3 ubiquitin ligase, which resulted in p53 accumulation and inhibition of cancer cell proliferation. As lung cancer cells usually express high levels of Toll-like receptor 9 (TLR9), we conjugated RPL32 small interfering RNA (siRNA) to the TLR9 ligand CpG to generate CpG-RPL32 siRNA, which could stabilize and guide RPL32 siRNA to lung cancer cells. Excitingly, CpG-RPL32 siRNA displayed strong anticancer abilities in lung cancer xenografts. Therefore, RPL32 is expected to be a potential target for lung cancer treatment.
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spelling pubmed-72815102020-06-11 RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation Xie, Jiansheng Zhang, Wei Liang, Xiaojing Shuai, Chong Zhou, Yubin Pan, Hongming Yang, Yunhai Han, Weidong Mol Ther Nucleic Acids Article Lung cancer is the leading cause of cancer death worldwide, and the overall survival rate of advanced lung cancer patients is unsatisfactory. Ribosomal proteins (RPs) play important roles in carcinogenesis. However, the role of RPL32 in lung cancer has not been demonstrated. Here, we report that RPL32 is aberrantly, highly expressed in lung cancer tissues and that the overexpression of RPL32 is correlated with the poor prognosis of these patients. RPL32 silencing significantly inhibited the proliferation of lung cancer cells, with an observed p53 accumulation and cell-cycle arrest. Mechanistically, knockdown of RPL32 resulted in ribosomal stress and affected rRNA maturation. RPL5 and RPL11 sensed stress and translocated from the nucleus to the nucleoplasm, where they bound to murine double minute 2 (MDM2), an important p53 E3 ubiquitin ligase, which resulted in p53 accumulation and inhibition of cancer cell proliferation. As lung cancer cells usually express high levels of Toll-like receptor 9 (TLR9), we conjugated RPL32 small interfering RNA (siRNA) to the TLR9 ligand CpG to generate CpG-RPL32 siRNA, which could stabilize and guide RPL32 siRNA to lung cancer cells. Excitingly, CpG-RPL32 siRNA displayed strong anticancer abilities in lung cancer xenografts. Therefore, RPL32 is expected to be a potential target for lung cancer treatment. American Society of Gene & Cell Therapy 2020-05-21 /pmc/articles/PMC7281510/ /pubmed/32516735 http://dx.doi.org/10.1016/j.omtn.2020.05.019 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Xie, Jiansheng
Zhang, Wei
Liang, Xiaojing
Shuai, Chong
Zhou, Yubin
Pan, Hongming
Yang, Yunhai
Han, Weidong
RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation
title RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation
title_full RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation
title_fullStr RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation
title_full_unstemmed RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation
title_short RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation
title_sort rpl32 promotes lung cancer progression by facilitating p53 degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281510/
https://www.ncbi.nlm.nih.gov/pubmed/32516735
http://dx.doi.org/10.1016/j.omtn.2020.05.019
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