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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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/d67a3e648dc44e669615a185ce786683 |
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| Sumario: | 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 |
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