2. Academic Validation
  3. P65-Driven MIR4435-2HG Enhances Prognostic Value and Mediates Oxaliplatin Resistance via the miR-378G/ABCB9 Axis in Colorectal Cancer

P65-Driven MIR4435-2HG Enhances Prognostic Value and Mediates Oxaliplatin Resistance via the miR-378G/ABCB9 Axis in Colorectal Cancer

  • Macromol Biosci. 2025 Jun 10:e00663. doi: 10.1002/mabi.202400663.
Xiaopeng Zhuang 1 2,  Jinji Jin 1,  Jun Cheng 1,  Zhejing Chen 1,  Weijian Zhu 3,  Xielin Huang 1,  Jiancheng Sun 1,  Chengyin Lin 1,  Qiantong Dong 1,  Dongwang Yan 2,  Xiaoliang Qi 4,  Wenyi Wu 1
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4 National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
PMID: 40493018 DOI: 10.1002/mabi.202400663
Abstract

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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