The IKKα-regulated microRNA miR-9-5p mediates lung cancer growth and invasiveness via CDH1/Wnt/β-catenin signalling
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.
Authors
- Evangelos Kolettas (ORCID: https://orcid.org/0000-0002-5820-487X)
- Spyros Foutadakis (ORCID: https://orcid.org/0000-0001-9161-1605)
- Christos Polytarchou (ORCID: https://orcid.org/0000-0002-1948-7934)
- Raphael Sandaltzopoulos (ORCID: https://orcid.org/0000-0002-8490-4300)
- Dimitris Thanos (ORCID: https://orcid.org/0000-0003-4288-3027)
- Maria Tokamani
- Dimitris C. Kanellis (ORCID: https://orcid.org/0000-0001-8690-2010)
- Maria Hatziapostolou (ORCID: https://orcid.org/0000-0003-2493-7028)
- Zoi Kanaki (ORCID: https://orcid.org/0000-0003-4661-5214)
- Giannis Vatsellas (ORCID: https://orcid.org/0000-0002-1631-1060)
- Apostolos Klinakis (ORCID: https://orcid.org/0000-0002-3923-861X)
- Eugenia Roupakia (ORCID: https://orcid.org/0000-0001-5573-1175)
- Alessandro Barbon (ORCID: https://orcid.org/0000-0002-1127-7764)
- Jiří Bártek (ORCID: https://orcid.org/0000-0003-2013-7525)
- Mark Samuels
- Simoni Besta (ORCID: https://orcid.org/0009-0000-8185-5083)
Institutions
- University of Nottingham (GB)
- Democritus University of Thrace (GR)
- University of Sussex (GB)
- University of Ioannina (GR)
- National and Kapodistrian University of Athens (GR)
- Academy of Athens (GR)
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
- Biomedical Research Foundation of the Academy of Athens (GR)
- Danish Cancer Society (DK)
- Nottingham Trent University (GB)
- University of Brescia (IT)
Publication Details
- Journal
- Cell Death Discovery
- Published
- 2026-06-17
- DOI
- https://doi.org/10.1038/s41420-026-03195-8
- Primary Topic
- MicroRNA in disease regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission