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

Abstract

Background

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

Disclosure

The authors report no conflicts of interest in this work.