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MNX1-AS1 suppresses chemosensitivity by activating the PI3K/AKT pathway in breast cancer

You Shuai1, Zhonghua Ma2, Jian Yue3

  • 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

International Journal of Biological Sciences
|June 16, 2025
PubMed

Insights

Long noncoding RNA MNX1-AS1 promotes paclitaxel resistance in breast cancer by activating the ITGA6/PI3K/AKT pathway. Targeting MNX1-AS1 offers a potential strategy to improve chemotherapy efficacy in breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) play a crucial role in cancer development and drug resistance.
  • The specific functions of lncRNAs in breast cancer (BC) and their mechanisms in drug resistance are not fully understood.

Purpose of the Study:

  • To investigate the role of MNX1-AS1 in breast cancer progression and paclitaxel resistance.
  • To elucidate the molecular mechanisms by which MNX1-AS1 influences chemoresistance.

Main Methods:

  • Quantitative real-time PCR to measure MNX1-AS1 expression.
  • Western blotting to assess protein levels.
  • RNA immunoprecipitation and luciferase reporter assays to study molecular interactions.
  • In vivo studies using tumor-bearing mice treated with MNX1-AS1 siRNA delivered via lipid nanoparticles.

Main Results:

  • MNX1-AS1 is significantly upregulated in breast cancer and associated with poor prognosis.
  • MNX1-AS1 promotes paclitaxel resistance by upregulating ITGA6 expression via both transcriptional and post-transcriptional mechanisms.
  • MNX1-AS1 interacts with YBX1 and IGF2BP2 to stabilize ITGA6, activating the PI3K/AKT pathway.
  • Delivery of MNX1-AS1 siRNA using lipid nanoparticles demonstrated significant antitumor effects in vivo.

Conclusions:

  • MNX1-AS1 drives breast cancer progression and chemoresistance by activating the ITGA6/PI3K/AKT pathway.
  • Targeting MNX1-AS1 presents a promising therapeutic approach to overcome paclitaxel resistance in breast cancer.
Keywords:
ITGA6/PI3K/AKT pathwayLncRNAbreast cancerchemosensitivitylipid nanoparticles

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