lncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance

Mao Cai,* Wanle Hu,* Chongjie Huang, Chongjun Zhou, Jiante Li, Yanyu Chen, Yaojun Yu Department of Anorectal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of China*These authors contributed equally to this...

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Autores principales: Cai M, Hu W, Huang C, Zhou C, Li J, Chen Y, Yu Y
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:d67a3e648dc44e669615a185ce7866832021-11-21T19:08:51ZlncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance1179-1322https://doaj.org/article/d67a3e648dc44e669615a185ce7866832021-11-01T00:00:00Zhttps://www.dovepress.com/lncrna-mcf2l-as1mir-105-il-1-axis-regulates-colorectal-cancer-cell-oxa-peer-reviewed-fulltext-article-CMARhttps://doaj.org/toc/1179-1322Mao Cai,* Wanle Hu,* Chongjie Huang, Chongjun Zhou, Jiante Li, Yanyu Chen, Yaojun Yu Department of Anorectal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaojun YuDepartment of Anorectal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, 325027, Zhejiang, People’s Republic of ChinaEmail yuyaojun8@sohu.comBackground: Interactions between non-coding RNAs and mRNAs have been shown to play key roles in colorectal cancer (CRC) resistance to chemotherapeutic drugs, but the regulatory network of these ncRNA/mRNA interactions in the context of CRC cell resistance to oxaliplatin has yet to be fully defined.Methods: MCF2L-AS1, miR-105, and IL-1β expression levels were measured in cells and serum samples via qPCR, while ELISAs were additionally used to quantify IL-1β levels in these samples. Interactions between MCF2L-AS1, miR-105, and IL-1β were detected through pull-down, RNA immunoprecipitation, and luciferase reporter assays. Cellular viability and OXA IC50 values were established through MTT assays, while in vivo OXA resistance was assessed using a tumor xenograft model system.Results: MCF2L-AS1 levels were significantly elevated in CRC patients that did not respond to chemotherapy and in CRC/OXA cells relative to responders and chemosensitive CRC cells. From a mechanistic perspective, miR-105 was identified as a MCF2L-AS1 target, with this miRNA, in turn, suppressing the expression of IL-1β. Knocking down MCF2L-AS1 or overexpressing miR-105 was sufficient to alleviate CRC/OXA cell chemoresistance, while overexpressing IL-1β reversed this effect.Conclusion: The MCF2L-AS1/miR-105/IL-1β regulatory axis regulates the resistance of CRC cells to OXA treatment.Keywords: CRC, oxaliplatin, OXA resistance, MCF2L-AS1, miR-105, IL-1&#x03B2Cai MHu WHuang CZhou CLi JChen YYu YDove Medical Pressarticlecrcoxaliplatinoxa resistancemcf2l-as1mir-105il-1bNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Management and Research, Vol Volume 13, Pp 8685-8694 (2021)
institution DOAJ
collection DOAJ
language EN
topic crc
oxaliplatin
oxa resistance
mcf2l-as1
mir-105
il-1b
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle crc
oxaliplatin
oxa resistance
mcf2l-as1
mir-105
il-1b
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cai M
Hu W
Huang C
Zhou C
Li J
Chen Y
Yu Y
lncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance
description Mao Cai,* Wanle Hu,* Chongjie Huang, Chongjun Zhou, Jiante Li, Yanyu Chen, Yaojun Yu Department of Anorectal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaojun YuDepartment of Anorectal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, 325027, Zhejiang, People’s Republic of ChinaEmail yuyaojun8@sohu.comBackground: Interactions between non-coding RNAs and mRNAs have been shown to play key roles in colorectal cancer (CRC) resistance to chemotherapeutic drugs, but the regulatory network of these ncRNA/mRNA interactions in the context of CRC cell resistance to oxaliplatin has yet to be fully defined.Methods: MCF2L-AS1, miR-105, and IL-1β expression levels were measured in cells and serum samples via qPCR, while ELISAs were additionally used to quantify IL-1β levels in these samples. Interactions between MCF2L-AS1, miR-105, and IL-1β were detected through pull-down, RNA immunoprecipitation, and luciferase reporter assays. Cellular viability and OXA IC50 values were established through MTT assays, while in vivo OXA resistance was assessed using a tumor xenograft model system.Results: MCF2L-AS1 levels were significantly elevated in CRC patients that did not respond to chemotherapy and in CRC/OXA cells relative to responders and chemosensitive CRC cells. From a mechanistic perspective, miR-105 was identified as a MCF2L-AS1 target, with this miRNA, in turn, suppressing the expression of IL-1β. Knocking down MCF2L-AS1 or overexpressing miR-105 was sufficient to alleviate CRC/OXA cell chemoresistance, while overexpressing IL-1β reversed this effect.Conclusion: The MCF2L-AS1/miR-105/IL-1β regulatory axis regulates the resistance of CRC cells to OXA treatment.Keywords: CRC, oxaliplatin, OXA resistance, MCF2L-AS1, miR-105, IL-1&#x03B2
format article
author Cai M
Hu W
Huang C
Zhou C
Li J
Chen Y
Yu Y
author_facet Cai M
Hu W
Huang C
Zhou C
Li J
Chen Y
Yu Y
author_sort Cai M
title lncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance
title_short lncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance
title_full lncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance
title_fullStr lncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance
title_full_unstemmed lncRNA MCF2L-AS1/miR-105/ IL-1β Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance
title_sort lncrna mcf2l-as1/mir-105/ il-1β axis regulates colorectal cancer cell oxaliplatin resistance
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/d67a3e648dc44e669615a185ce786683
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AT lij lncrnamcf2las1mir105il1betaaxisregulatescolorectalcancercelloxaliplatinresistance
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