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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Cancer Molecular Targets and Therapeutics

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1606933

This article is part of the Research TopicThe Role of Circular RNAs and MicroRNAs in Non-Small Cell Lung Cancer: From Mechanisms to Therapeutic PotentialView all 4 articles

Prognostic impact of miR-17-5p and miR-20a-5p in NSCLC diverge in subgroups according to lymph node status

Provisionally accepted
Dagny  FørdeDagny Førde1*Thomas  KilværThomas Kilvær1,2Mona  Irene PedersenMona Irene Pedersen1Ana  Paola LombardiAna Paola Lombardi1Irene  D’arsièIrene D’arsiè3Erna-Elise  PaulsenErna-Elise Paulsen1,2Lill-Tove  Rasmussen BusundLill-Tove Rasmussen Busund1,2Mehrdad  RakaeeMehrdad Rakaee1,4Tom  DonnemTom Donnem1,2Sigve  AndersenSigve Andersen1,2
  • 1UiT The Arctic University of Norway, Tromsø, Norway
  • 2University Hospital of North Norway, Tromsø, Troms, Norway
  • 3University of Trento, Trento, Trentino-Alto Adige/Südtirol, Italy
  • 4University of Oslo, Oslo, Oslo, Norway

The final, formatted version of the article will be published soon.

MicroRNAs (miRs) are short non-coding, functional RNA molecules which regulate gene expression. Different miRs are frequently dysregulated and implicated in the development and outcome of non-small cell lung cancer (NSCLC). We investigated the prognostic and functional aspects of miR-17-5p and miR-20a-5p by in situ hybridization in a large, well-characterized cohort of resected NSCLC patients, and through overexpression in two NSCLC cell lines. In the overall cohort, we observed no prognostic impact of miR-17-5p and miR-20a-5p in univariate analyses, while high expression of miR-20a-5p was associated with a positive outcome in multivariate analysis (HR 0.732, 95% CI 0.544-0.986, P = 0.040). In subgroup analyses, high expression of miR-20a-5p was associated with a positive prognosis in patients with lung squamous cell carcinoma and lymph node metastases (N+). Interestingly, miR-17-5p was associated with a poor prognosis in patients without lymph node metastases (N0), while no prognostic impact was observed in N+ patients. In cell line studies, overexpression of miR-17-5p did not influence proliferation but lead to increased invasion in both investigated cell lines. Overexpression of miR-20a-5p led to decreased proliferation in one of two investigated cell lines and, like miR-17-5p, increased invasion. Overall, our results suggest that the prognostic role of miR-17-5p and miR-20a-5p in early-stage NSCLC is context-dependent. Consequently, further studies are needed to elucidate the role of these miRs during NSCLC carcinogenesis. Clinical implementation should not be initiated until their role in different disease settings is sufficiently understood.

Keywords: NSCLC, miR-17, miR-20, prognosis, cell lines, digital pathology

Received: 06 Apr 2025; Accepted: 09 Sep 2025.

Copyright: © 2025 Førde, Kilvær, Pedersen, Lombardi, D’arsiè, Paulsen, Busund, Rakaee, Donnem and Andersen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dagny Førde, UiT The Arctic University of Norway, Tromsø, Norway

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