Cargando…

LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer

Dysregulation of long non-coding RNAs (LncRNAs) participated into the initiation and progression of different diseases via direct regulation of proteins or indirect regulation of microRNA (miRNA)-target genes. LINC00473 is a novel carcinoma-related LncRNA and up-regulated in many cancers for tumor g...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Lin, Zhang, Xufeng, Sheng, Li, Qiu, Chun, Luo, Rongcheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147912/
https://www.ncbi.nlm.nih.gov/pubmed/30126852
http://dx.doi.org/10.1042/BSR20180790
_version_ 1783356655504719872
author Wang, Lin
Zhang, Xufeng
Sheng, Li
Qiu, Chun
Luo, Rongcheng
author_facet Wang, Lin
Zhang, Xufeng
Sheng, Li
Qiu, Chun
Luo, Rongcheng
author_sort Wang, Lin
collection PubMed
description Dysregulation of long non-coding RNAs (LncRNAs) participated into the initiation and progression of different diseases via direct regulation of proteins or indirect regulation of microRNA (miRNA)-target genes. LINC00473 is a novel carcinoma-related LncRNA and up-regulated in many cancers for tumor growth and metastasis, but its role in chemotherapy resistance is unclear. We here investigated the function of LINC00473 in colorectal cancer (CRC) in vitro and in vivo. The CRC tissues (n=20) and relative normal tissues were collected and found that LINC00473 was overexpressed in CRC tissues when compared with which in normal tissues. Highly expressed LINC00473 predicted large tumor size, high TNM stage of CRC patients. Interestingly, the tumor suppressor miR-15a was down-regulated and negatively correlated with LINC00473 levels in CRC. LINC00473 harbored the binding sites for miR-15a and reduced its availability in CRC cell line HCT116. Knockdown of LINC00473 elevated the expression of miR-15a. Moreover, in the Taxol-resistant HCT116, the LINC00473 level was further increased than that in HCT116. Knockdown of LINC00473 restored the Taxol-induced cytotoxicity, inhibited the cell vitality, colony formation and induced apoptosis, impaired the ability of migration or invasion, but these effects could be abrogated by the inhibition of miR-15a. Mechanistically, the BCL-2-related anti-apoptosis pathway was activated and the multidrug-resistant (MDR) genes LRP, MDR1 were up-regulated by LINC00473. Furthermore, inhibition of LINC00473 in vivo could overcome the Taxol resistance of CRC cells, could recover the expression of tumor suppressor miR-15a and chemotherapy-induced tumor regression, indicating that LINC00473 functioned as oncogene in CRC via miR-15a.
format Online
Article
Text
id pubmed-6147912
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-61479122018-09-25 LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer Wang, Lin Zhang, Xufeng Sheng, Li Qiu, Chun Luo, Rongcheng Biosci Rep Research Articles Dysregulation of long non-coding RNAs (LncRNAs) participated into the initiation and progression of different diseases via direct regulation of proteins or indirect regulation of microRNA (miRNA)-target genes. LINC00473 is a novel carcinoma-related LncRNA and up-regulated in many cancers for tumor growth and metastasis, but its role in chemotherapy resistance is unclear. We here investigated the function of LINC00473 in colorectal cancer (CRC) in vitro and in vivo. The CRC tissues (n=20) and relative normal tissues were collected and found that LINC00473 was overexpressed in CRC tissues when compared with which in normal tissues. Highly expressed LINC00473 predicted large tumor size, high TNM stage of CRC patients. Interestingly, the tumor suppressor miR-15a was down-regulated and negatively correlated with LINC00473 levels in CRC. LINC00473 harbored the binding sites for miR-15a and reduced its availability in CRC cell line HCT116. Knockdown of LINC00473 elevated the expression of miR-15a. Moreover, in the Taxol-resistant HCT116, the LINC00473 level was further increased than that in HCT116. Knockdown of LINC00473 restored the Taxol-induced cytotoxicity, inhibited the cell vitality, colony formation and induced apoptosis, impaired the ability of migration or invasion, but these effects could be abrogated by the inhibition of miR-15a. Mechanistically, the BCL-2-related anti-apoptosis pathway was activated and the multidrug-resistant (MDR) genes LRP, MDR1 were up-regulated by LINC00473. Furthermore, inhibition of LINC00473 in vivo could overcome the Taxol resistance of CRC cells, could recover the expression of tumor suppressor miR-15a and chemotherapy-induced tumor regression, indicating that LINC00473 functioned as oncogene in CRC via miR-15a. Portland Press Ltd. 2018-09-21 /pmc/articles/PMC6147912/ /pubmed/30126852 http://dx.doi.org/10.1042/BSR20180790 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, Lin
Zhang, Xufeng
Sheng, Li
Qiu, Chun
Luo, Rongcheng
LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer
title LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer
title_full LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer
title_fullStr LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer
title_full_unstemmed LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer
title_short LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer
title_sort linc00473 promotes the taxol resistance via mir-15a in colorectal cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147912/
https://www.ncbi.nlm.nih.gov/pubmed/30126852
http://dx.doi.org/10.1042/BSR20180790
work_keys_str_mv AT wanglin linc00473promotesthetaxolresistanceviamir15aincolorectalcancer
AT zhangxufeng linc00473promotesthetaxolresistanceviamir15aincolorectalcancer
AT shengli linc00473promotesthetaxolresistanceviamir15aincolorectalcancer
AT qiuchun linc00473promotesthetaxolresistanceviamir15aincolorectalcancer
AT luorongcheng linc00473promotesthetaxolresistanceviamir15aincolorectalcancer