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Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway

Guanine nucleotide-binding protein-like-3-like (GNL3L) is a crucial regulator of NF-κB signaling that is aberrantly activated during diverse chemoresistance-associated cellular processes. However, the molecular mechanisms of GNL3L tumor initiation and resistant state are largely unknown. Moreover, t...

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Autores principales: Kannathasan, Thetchinamoorthy, Kuo, Wei-Wen, Chen, Ming-Cheng, Viswanadha, Vijaya Padma, Shen, Chia-Yao, Tu, Chuan-Chou, Yeh, Yu-Lan, Bharath, Mahalakshmi, Shibu, Marthandam Asokan, Huang, Chih-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281507/
https://www.ncbi.nlm.nih.gov/pubmed/32422901
http://dx.doi.org/10.3390/cancers12051231
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author Kannathasan, Thetchinamoorthy
Kuo, Wei-Wen
Chen, Ming-Cheng
Viswanadha, Vijaya Padma
Shen, Chia-Yao
Tu, Chuan-Chou
Yeh, Yu-Lan
Bharath, Mahalakshmi
Shibu, Marthandam Asokan
Huang, Chih-Yang
author_facet Kannathasan, Thetchinamoorthy
Kuo, Wei-Wen
Chen, Ming-Cheng
Viswanadha, Vijaya Padma
Shen, Chia-Yao
Tu, Chuan-Chou
Yeh, Yu-Lan
Bharath, Mahalakshmi
Shibu, Marthandam Asokan
Huang, Chih-Yang
author_sort Kannathasan, Thetchinamoorthy
collection PubMed
description Guanine nucleotide-binding protein-like-3-like (GNL3L) is a crucial regulator of NF-κB signaling that is aberrantly activated during diverse chemoresistance-associated cellular processes. However, the molecular mechanisms of GNL3L tumor initiation and resistant state are largely unknown. Moreover, the identification of predictive biomarkers is necessary to effectively generate therapeutic strategies for metastatic human colorectal cancer (CRC). This study aims to identify how cells acquire resistance to anticancer drugs and whether the downregulation of miR-4454 is associated with the progression of CRC. Here, we have shown that the overexpression of miR-4454 in resistant tumors is a crucial precursor for the posttranscriptional repression of GNL3L in human chemoresistant CRC progression, and we used doxycycline induced miR-4454 overexpression that significantly reduced tumor volume in a subcutaneous injection nude mice model. Together, these observations highlight that the downregulation of miR-4454 in resistant clones is prominently responsible for maintaining their resistance against anticancer drug therapy. Our study indicates that the development of miR-4454 as a microRNA-based therapeutic approach to silence GNL3L may remarkably reduce oncogenic cell survival that depends on GNL3L/NF-κB signaling, making miR-4454 a candidate for treating metastatic human CRC.
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spelling pubmed-72815072020-06-17 Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway Kannathasan, Thetchinamoorthy Kuo, Wei-Wen Chen, Ming-Cheng Viswanadha, Vijaya Padma Shen, Chia-Yao Tu, Chuan-Chou Yeh, Yu-Lan Bharath, Mahalakshmi Shibu, Marthandam Asokan Huang, Chih-Yang Cancers (Basel) Article Guanine nucleotide-binding protein-like-3-like (GNL3L) is a crucial regulator of NF-κB signaling that is aberrantly activated during diverse chemoresistance-associated cellular processes. However, the molecular mechanisms of GNL3L tumor initiation and resistant state are largely unknown. Moreover, the identification of predictive biomarkers is necessary to effectively generate therapeutic strategies for metastatic human colorectal cancer (CRC). This study aims to identify how cells acquire resistance to anticancer drugs and whether the downregulation of miR-4454 is associated with the progression of CRC. Here, we have shown that the overexpression of miR-4454 in resistant tumors is a crucial precursor for the posttranscriptional repression of GNL3L in human chemoresistant CRC progression, and we used doxycycline induced miR-4454 overexpression that significantly reduced tumor volume in a subcutaneous injection nude mice model. Together, these observations highlight that the downregulation of miR-4454 in resistant clones is prominently responsible for maintaining their resistance against anticancer drug therapy. Our study indicates that the development of miR-4454 as a microRNA-based therapeutic approach to silence GNL3L may remarkably reduce oncogenic cell survival that depends on GNL3L/NF-κB signaling, making miR-4454 a candidate for treating metastatic human CRC. MDPI 2020-05-14 /pmc/articles/PMC7281507/ /pubmed/32422901 http://dx.doi.org/10.3390/cancers12051231 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kannathasan, Thetchinamoorthy
Kuo, Wei-Wen
Chen, Ming-Cheng
Viswanadha, Vijaya Padma
Shen, Chia-Yao
Tu, Chuan-Chou
Yeh, Yu-Lan
Bharath, Mahalakshmi
Shibu, Marthandam Asokan
Huang, Chih-Yang
Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway
title Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway
title_full Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway
title_fullStr Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway
title_full_unstemmed Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway
title_short Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway
title_sort chemoresistance-associated silencing of mir-4454 promotes colorectal cancer aggression through the gnl3l and nf-κb pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281507/
https://www.ncbi.nlm.nih.gov/pubmed/32422901
http://dx.doi.org/10.3390/cancers12051231
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