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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Dove Medical Press
2021
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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𻋊i 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) |
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crc oxaliplatin oxa resistance mcf2l-as1 mir-105 il-1b Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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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 |
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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-1β |
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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