Cargando…
Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3
It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876302/ https://www.ncbi.nlm.nih.gov/pubmed/33585440 http://dx.doi.org/10.3389/fcell.2020.582723 |
_version_ | 1783649944065802240 |
---|---|
author | Chen, Xijuan Liu, Yingqiang Zhang, Qinglan Liu, Baoxing Cheng, Yan Zhang, Yonglei Sun, Yanan Liu, Junqi Gen, Hong |
author_facet | Chen, Xijuan Liu, Yingqiang Zhang, Qinglan Liu, Baoxing Cheng, Yan Zhang, Yonglei Sun, Yanan Liu, Junqi Gen, Hong |
author_sort | Chen, Xijuan |
collection | PubMed |
description | It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the underlying mechanisms. High expression of HOTTIP was detected in mitomycin-resistant CRC cells. Inhibition of HOTTIP reduced the mitomycin resistance. In the co-culture system of mitomycin-resistant cells or their derived exosomes with CRC cells, the HOTTIP was found to be transferred into the parental cells via extracellular vesicles (EVs) secreted from mitomycin-resistant cells and to contribute to the mitomycin resistance. Based on the bioinformatics databases, possible interaction network of HOTTIP, microRNA-214 (miR-214) and Karyopherin subunit alpha 3 (KPNA3) in CRC was predicted, which was further analyzed by dual-luciferase reporter, RNA binding protein immunoprecipitation and RNA pull-down assays. As HOTTIP down-regulated miR-214 to elevate the KPNA3 expression, HOTTIP enhanced the mitomycin resistance through impairing miR-214-dependent inhibition of KPNA3. Finally, HOTTIP was suggested as an independent factor predicting mitomycin response in patients with CRC. Those data together confirmed the promotive effects of EV-carried HOTTIP on the mitomycin resistance, while targeting HOTTIP might be a promising strategy overcoming drug resistance in CRC. |
format | Online Article Text |
id | pubmed-7876302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78763022021-02-12 Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3 Chen, Xijuan Liu, Yingqiang Zhang, Qinglan Liu, Baoxing Cheng, Yan Zhang, Yonglei Sun, Yanan Liu, Junqi Gen, Hong Front Cell Dev Biol Cell and Developmental Biology It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the underlying mechanisms. High expression of HOTTIP was detected in mitomycin-resistant CRC cells. Inhibition of HOTTIP reduced the mitomycin resistance. In the co-culture system of mitomycin-resistant cells or their derived exosomes with CRC cells, the HOTTIP was found to be transferred into the parental cells via extracellular vesicles (EVs) secreted from mitomycin-resistant cells and to contribute to the mitomycin resistance. Based on the bioinformatics databases, possible interaction network of HOTTIP, microRNA-214 (miR-214) and Karyopherin subunit alpha 3 (KPNA3) in CRC was predicted, which was further analyzed by dual-luciferase reporter, RNA binding protein immunoprecipitation and RNA pull-down assays. As HOTTIP down-regulated miR-214 to elevate the KPNA3 expression, HOTTIP enhanced the mitomycin resistance through impairing miR-214-dependent inhibition of KPNA3. Finally, HOTTIP was suggested as an independent factor predicting mitomycin response in patients with CRC. Those data together confirmed the promotive effects of EV-carried HOTTIP on the mitomycin resistance, while targeting HOTTIP might be a promising strategy overcoming drug resistance in CRC. Frontiers Media S.A. 2021-01-28 /pmc/articles/PMC7876302/ /pubmed/33585440 http://dx.doi.org/10.3389/fcell.2020.582723 Text en Copyright © 2021 Chen, Liu, Zhang, Liu, Cheng, Zhang, Sun, Liu and Gen. 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 | Cell and Developmental Biology Chen, Xijuan Liu, Yingqiang Zhang, Qinglan Liu, Baoxing Cheng, Yan Zhang, Yonglei Sun, Yanan Liu, Junqi Gen, Hong Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3 |
title | Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3 |
title_full | Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3 |
title_fullStr | Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3 |
title_full_unstemmed | Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3 |
title_short | Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3 |
title_sort | exosomal long non-coding rna hottip increases resistance of colorectal cancer cells to mitomycin via impairing mir-214-mediated degradation of kpna3 |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876302/ https://www.ncbi.nlm.nih.gov/pubmed/33585440 http://dx.doi.org/10.3389/fcell.2020.582723 |
work_keys_str_mv | AT chenxijuan exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT liuyingqiang exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT zhangqinglan exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT liubaoxing exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT chengyan exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT zhangyonglei exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT sunyanan exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT liujunqi exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 AT genhong exosomallongnoncodingrnahottipincreasesresistanceofcolorectalcancercellstomitomycinviaimpairingmir214mediateddegradationofkpna3 |