RRM2‑mediated Wnt/β‑catenin signaling pathway activation in lung adenocarcinoma: A potential prognostic biomarker

Jiang,Yongjie; Hu,Xing; Pang,Min; Huang,Yuyan; Ren,Bi; He,Liping; Jiang,Li

doi:10.3892/ol.2023.14003

RRM2‑mediated Wnt/β‑catenin signaling pathway activation in lung adenocarcinoma: A potential prognostic biomarker

Authors:
- Yongjie Jiang
- Xing Hu
- Min Pang
- Yuyan Huang
- Bi Ren
- Liping He
- Li Jiang
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Affiliations: Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: August 10, 2023 https://doi.org/10.3892/ol.2023.14003
Article Number: 417
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the role and mechanism of action of ribonucleotide reductase M2 (RRM2) in lung adenocarcinoma and its potential as a therapeutic target. Data of patients with lung adenocarcinoma from The Cancer Genome Atlas database were collected and analyzed to evaluate the potential of RRM2 as a biomarker. The expression of RRM2 was evaluated in the A549 cell line and its cisplatin‑resistant A549/DDP cell line derivative by western blot and reverse transcription‑quantitative PCR. The study also investigated cell proliferation and the mechanism by which RRM2 controls cellular cisplatin resistance using CCK‑8 and colony‑formation assays. In addition, cell migration was assessed using Transwell assays, and the cell cycle and apoptosis were examined using flow cytometry. RRM2 was highly expressed in lung adenocarcinoma and was associated with the clinical TMN stage. Functional enrichment analysis showed that RRM2 was enriched in the cell cycle. Immune cell infiltration analysis identified 12 types of immune cell that exhibited differences between patients expressing different levels of RRM2. Cellular assays revealed higher levels of RRM2 expression in A549/DDP cells than A549 cells, and its expression was induced by cisplatin. RRM2 knockdown decreased cell proliferation and migration, accelerated apoptosis and caused cell cycle arrest in the S‑phase, increasing the sensitivity of A549 and A549/DDP cells to cisplatin through the Wnt/β‑catenin signaling pathway. Overexpression of β‑catenin reduced the effects of RRM2 knockdown on A549 cells. Lung adenocarcinoma growth may be influenced by RRM2 through the Wnt/β‑catenin signaling pathway, suggesting a potential pathway for cancer progression.

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