2. Academic Validation
  3. The IKKα-regulated microRNA miR-9-5p mediates lung cancer growth and invasiveness via CDH1/Wnt/β-catenin signalling

The IKKα-regulated microRNA miR-9-5p mediates lung cancer growth and invasiveness via CDH1/Wnt/β-catenin signalling

  • Cell Death Discov. 2026 Jun 17. doi: 10.1038/s41420-026-03195-8.
Simoni Besta 1 2,  Eugenia Roupakia 1 2,  Zoi Kanaki 3,  Giannis Vatsellas 4,  Mark Samuels 5,  Spyros Foutadakis 6,  Maria Tokamani 7,  Alessandro Barbon 8,  Raphael Sandaltzopoulos 7,  Dimitris C Kanellis 9,  Jiri Bartek 9 10,  Maria Hatziapostolou 11,  Christos Polytarchou 11,  Dimitris Thanos 3 4,  Apostolos Klinakis 3,  Evangelos Kolettas 12 13
Affiliations

Affiliations

  • 1 Laboratory of Biology, School of Medicine, Faculty of Health Sciences, and Institute of Biosciences, Centre for Research and Innovation, University of Ioannina, University Campus, Ioannina, Greece.
  • 2 Biomedical Research Institute, Foundation for Research and Technology, University of Ioannina Campus, Ioannina, Greece.
  • 3 Centre of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
  • 4 Greek Genome Center, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
  • 5 Department of Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Brighton, UK.
  • 6 4th Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • 7 Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Thrace, Greece.
  • 8 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
  • 9 Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • 10 Genome Integrity, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark.
  • 11 Department of Biosciences, John van Geest Cancer Research Centre, Centre for Systems Health and Integrated Metabolic Research, School of Science and Technology, Nottingham Trent University, Nottingham, UK.
  • 12 Laboratory of Biology, School of Medicine, Faculty of Health Sciences, and Institute of Biosciences, Centre for Research and Innovation, University of Ioannina, University Campus, Ioannina, Greece. [email protected].
  • 13 Biomedical Research Institute, Foundation for Research and Technology, University of Ioannina Campus, Ioannina, Greece. [email protected].
PMID: 42303974 DOI: 10.1038/s41420-026-03195-8
Abstract

IKKα is a serine/threonine kinase that acts as a tumour suppressor in non-small cell lung Cancer (NSCLC) in an NF-κΒ-independent manner, however, little is known about its downstream signalling pathways. To interrogate the IKKα signalling network in NSCLC, we investigated the impact of IKKα silencing on the miRNA expression profile of NSCLC cells. Nanostring miRNome analysis identified miR-9-5p, a known oncomir, as the top upregulated miRNA upon IKKα depletion. We show that overexpression of miR-9-5p in human lung Cancer cells increases cell migration and invasion and promotes epithelial-to-mesenchymal cell transition (EMT) through loss of E-cadherin and activation of the Akt1/β-catenin pathway. In vivo tumour xenograft models show that overexpression of miR-9-5p promotes tumour growth and widespread transcriptomic reprogramming, altering the expression of genes related to EMT, Apoptosis and NF-κB signalling. Overall, we show that miR-9-5p acts as an oncogenic effector upon IKKα loss, promoting tumour progression through EMT and Akt-1/GSK-3β/β-catenin pathway activation, leading to increased invasiveness and tumour growth.

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