Cargando…

CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer

Gastric cancer (GC) remains a major world-wide challenge, especially in Asian countries. Chemotherapy with 5-fluorouracil (5-FU) and cisplatin is used as the first-line treatment and development of chemoresistance is a major cause of progression. UMP/CMP kinase is responsible for the phosphorylation...

Descripción completa

Detalles Bibliográficos
Autores principales: Chu, Huaizhu, Han, Nahui, Xu, Jianguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013733/
https://www.ncbi.nlm.nih.gov/pubmed/33816278
http://dx.doi.org/10.3389/fonc.2021.637470
_version_ 1783673515214372864
author Chu, Huaizhu
Han, Nahui
Xu, Jianguo
author_facet Chu, Huaizhu
Han, Nahui
Xu, Jianguo
author_sort Chu, Huaizhu
collection PubMed
description Gastric cancer (GC) remains a major world-wide challenge, especially in Asian countries. Chemotherapy with 5-fluorouracil (5-FU) and cisplatin is used as the first-line treatment and development of chemoresistance is a major cause of progression. UMP/CMP kinase is responsible for the phosphorylation of the ribonucleotide metabolite 5-fluoro-5′-monophosphate (FUMP) in 5-FU metabolic process, and recognized as a key step in the conversion of 5-FU to cytotoxic metabolites. Our bioinformatics analysis and molecular experiments demonstrated that high expression of CMPK1 was associated with prolonged survival and response to 5-FU treatment in GC samples. Further analysis demonstrated that miR-130b as a key epigenetic regulator of CMPK1, and miR-130b-mediated attenuation of CMPK1 resulted in resistance of gastric cancer cells to DNA damage and cell death after treatment with 5-FU. Rescue experiments with augmented CMPK1 expression abolished the effect of miR-130b demonstrating the key function of this miRNA in this pathway. Thus, this newly identified miR-130b-CMPK1 axis suggests a potentially new chemotherapeutic strategy for improved response to 5-FU therapy.
format Online
Article
Text
id pubmed-8013733
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-80137332021-04-02 CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer Chu, Huaizhu Han, Nahui Xu, Jianguo Front Oncol Oncology Gastric cancer (GC) remains a major world-wide challenge, especially in Asian countries. Chemotherapy with 5-fluorouracil (5-FU) and cisplatin is used as the first-line treatment and development of chemoresistance is a major cause of progression. UMP/CMP kinase is responsible for the phosphorylation of the ribonucleotide metabolite 5-fluoro-5′-monophosphate (FUMP) in 5-FU metabolic process, and recognized as a key step in the conversion of 5-FU to cytotoxic metabolites. Our bioinformatics analysis and molecular experiments demonstrated that high expression of CMPK1 was associated with prolonged survival and response to 5-FU treatment in GC samples. Further analysis demonstrated that miR-130b as a key epigenetic regulator of CMPK1, and miR-130b-mediated attenuation of CMPK1 resulted in resistance of gastric cancer cells to DNA damage and cell death after treatment with 5-FU. Rescue experiments with augmented CMPK1 expression abolished the effect of miR-130b demonstrating the key function of this miRNA in this pathway. Thus, this newly identified miR-130b-CMPK1 axis suggests a potentially new chemotherapeutic strategy for improved response to 5-FU therapy. Frontiers Media S.A. 2021-03-18 /pmc/articles/PMC8013733/ /pubmed/33816278 http://dx.doi.org/10.3389/fonc.2021.637470 Text en Copyright © 2021 Chu, Han and Xu http://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 Oncology
Chu, Huaizhu
Han, Nahui
Xu, Jianguo
CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer
title CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer
title_full CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer
title_fullStr CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer
title_full_unstemmed CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer
title_short CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer
title_sort cmpk1 regulated by mir-130b attenuates response to 5-fu treatment in gastric cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013733/
https://www.ncbi.nlm.nih.gov/pubmed/33816278
http://dx.doi.org/10.3389/fonc.2021.637470
work_keys_str_mv AT chuhuaizhu cmpk1regulatedbymir130battenuatesresponseto5futreatmentingastriccancer
AT hannahui cmpk1regulatedbymir130battenuatesresponseto5futreatmentingastriccancer
AT xujianguo cmpk1regulatedbymir130battenuatesresponseto5futreatmentingastriccancer