Long non-coding RNA MIR4435-2HG has emerged as a pivotal oncogenic factor across various cancers. However, its role in chemoresistance, particularly in colorectal cancer (CRC), remains unclear. This work demonstrates that MIR4435-2HG is significantly overexpressed in CRC tissues, correlating with poor prognosis and resistance to oxaliplatin (L-OHP) based chemotherapy. Mechanistically, MIR4435-2HG binds to miR-378g, leading to elevated ABCB9 levels, a crucial factor in drug resistance. Both in vitro and in vivo experiments indicate that the MIR4435-2HG/miR-378g/ABCB9 axis confers L-OHP resistance in CRC cells by reducing DNA damage and enhancing cell survival. Additionally, P65, a component of the NF-κB pathway, directly promotes MIR4435-2HG transcription, triggering subsequent chemoresistance. Based on these results, MIR4435-2HG is recognized as a reliable prognostic marker and serves as a target for therapeutic strategies, presenting new approaches to counteract L-OHP resistance and enhance CRC patient outcomes.
Keywords: ABCB9; L‐OHP; MIR4435‐2HG; colorectal cancer; miR‐378g; resistance.
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