Cargando…

Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer

One of the treatment failures for colorectal cancer (CRC) is resistance to chemotherapy drugs. miRNAs have been demonstrated to be a new regulator of pathobiological processes in various tumors. While few studies have explored the specific role of miR-141 in mediating 5-fluorouracil (5-FU) sensitivi...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Feifei, Zhao, Lianmei, Zhang, Juan, Meng, Zesong, Zhou, Chaoxi, Wang, Guanglin, Liu, Youqiang, Li, Meng, Xi, Jinchuan, Niu, Wenbo, Wang, Guiying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435556/
https://www.ncbi.nlm.nih.gov/pubmed/30429233
http://dx.doi.org/10.1042/BSR20180978
_version_ 1783406657507688448
author Wang, Feifei
Zhao, Lianmei
Zhang, Juan
Meng, Zesong
Zhou, Chaoxi
Wang, Guanglin
Liu, Youqiang
Li, Meng
Xi, Jinchuan
Niu, Wenbo
Wang, Guiying
author_facet Wang, Feifei
Zhao, Lianmei
Zhang, Juan
Meng, Zesong
Zhou, Chaoxi
Wang, Guanglin
Liu, Youqiang
Li, Meng
Xi, Jinchuan
Niu, Wenbo
Wang, Guiying
author_sort Wang, Feifei
collection PubMed
description One of the treatment failures for colorectal cancer (CRC) is resistance to chemotherapy drugs. miRNAs have been demonstrated to be a new regulator of pathobiological processes in various tumors. While few studies have explored the specific role of miR-141 in mediating 5-fluorouracil (5-FU) sensitivity of CRC cells, the present study aimed to detect the contribution of miR-141 in 5-FU sensitivity. The CRC cells viability was measured by MTS assay and cell colony forming. The expression of miR-141 and its downstream targets were assessed by reverse transcription quantitative PCR, Western blotting, and immunohistochemistry. The functional assays were conducted using CRC cells and nude mice. At the present study, we found overexpression of miR-141 could inhibit proliferation, migration, tumor-forming and invasive potential of CRC cells in vitro and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was verified as a directed target of miR-141. The combination treatment of miR-141 with 5-FU, directly targetting MAP4K4, could better inhibit invasion and metastasis of CRC cells colony than either one alone. Furthermore, overexpression of miR-141, targetting MAP4K4, enhanced the effected of 5-FU and suppressed the malignant biological behaviors, in vivo. Our findings showed that 5-FU inhibited malignant behavior of human CRC cells in vitro and in vivo by enhancing the efficiency of miR-141. Our data suggested that targetting the miR-141/MAP4K4 signaling pathway could be a potential molecular target that may enhance chemotherapeutic efficacy in the treatment of CRC.
format Online
Article
Text
id pubmed-6435556
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-64355562019-04-12 Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer Wang, Feifei Zhao, Lianmei Zhang, Juan Meng, Zesong Zhou, Chaoxi Wang, Guanglin Liu, Youqiang Li, Meng Xi, Jinchuan Niu, Wenbo Wang, Guiying Biosci Rep Research Articles One of the treatment failures for colorectal cancer (CRC) is resistance to chemotherapy drugs. miRNAs have been demonstrated to be a new regulator of pathobiological processes in various tumors. While few studies have explored the specific role of miR-141 in mediating 5-fluorouracil (5-FU) sensitivity of CRC cells, the present study aimed to detect the contribution of miR-141 in 5-FU sensitivity. The CRC cells viability was measured by MTS assay and cell colony forming. The expression of miR-141 and its downstream targets were assessed by reverse transcription quantitative PCR, Western blotting, and immunohistochemistry. The functional assays were conducted using CRC cells and nude mice. At the present study, we found overexpression of miR-141 could inhibit proliferation, migration, tumor-forming and invasive potential of CRC cells in vitro and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was verified as a directed target of miR-141. The combination treatment of miR-141 with 5-FU, directly targetting MAP4K4, could better inhibit invasion and metastasis of CRC cells colony than either one alone. Furthermore, overexpression of miR-141, targetting MAP4K4, enhanced the effected of 5-FU and suppressed the malignant biological behaviors, in vivo. Our findings showed that 5-FU inhibited malignant behavior of human CRC cells in vitro and in vivo by enhancing the efficiency of miR-141. Our data suggested that targetting the miR-141/MAP4K4 signaling pathway could be a potential molecular target that may enhance chemotherapeutic efficacy in the treatment of CRC. Portland Press Ltd. 2018-12-21 /pmc/articles/PMC6435556/ /pubmed/30429233 http://dx.doi.org/10.1042/BSR20180978 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Wang, Feifei
Zhao, Lianmei
Zhang, Juan
Meng, Zesong
Zhou, Chaoxi
Wang, Guanglin
Liu, Youqiang
Li, Meng
Xi, Jinchuan
Niu, Wenbo
Wang, Guiying
Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer
title Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer
title_full Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer
title_fullStr Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer
title_full_unstemmed Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer
title_short Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer
title_sort chemotherapy-induced mir-141/map4k4 signaling suppresses progression of colorectal cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435556/
https://www.ncbi.nlm.nih.gov/pubmed/30429233
http://dx.doi.org/10.1042/BSR20180978
work_keys_str_mv AT wangfeifei chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT zhaolianmei chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT zhangjuan chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT mengzesong chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT zhouchaoxi chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT wangguanglin chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT liuyouqiang chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT limeng chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT xijinchuan chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT niuwenbo chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer
AT wangguiying chemotherapyinducedmir141map4k4signalingsuppressesprogressionofcolorectalcancer