Significance of Ribonucleoside-diphosphate Reductase Subunit M2 in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) bioinformatic analyses experimental validation molecular biomarker ribonucleoside-diphosphate reductase subunit M2 (RRM2)

Journal

Current gene therapy
ISSN: 1875-5631
Titre abrégé: Curr Gene Ther
Pays: United Arab Emirates
ID NLM: 101125446

Informations de publication

Date de publication:
12 Jun 2024
Historique:
received: 09 10 2023
revised: 22 04 2024
accepted: 23 04 2024
medline: 26 6 2024
pubmed: 26 6 2024
entrez: 26 6 2024
Statut: aheadofprint

Résumé

The Ribonucleoside-diphosphate Reductase subunit M2 (RRM2) is known to be overexpressed in various cancers, though its specific functional implications remain unclear. This aims to elucidate the role of RRM2 in the progression of Lung Adenocarcinoma (LUAD) by exploring its involvement and potential impact. RRM2 data were sourced from multiple databases to assess its diagnostic and prognostic significance in LUAD. We evaluated the association between RRM2 expression and immune cell infiltration, analyzed its function, and explored the effects of modulating RRM2 expression on LUAD cell characteristics through laboratory experiments. RRM2 was significantly upregulated in LUAD tissues and cells compared to normal counterparts (p<0.05), with rare genetic alterations noted (approximately 2%). This overexpression clearly distinguished LUAD from normal tissue (area under the curve (AUC): 0.963, 95% confidence intervals (CI): 0.946-0.981). Elevated RRM2 expression was significantly associated with adverse clinicopathological characteristics and poor prognosis in LUAD patients. Furthermore, a positive association was observed between RRM2 expression and immune cell infiltration. Pathway analysis revealed a critical connection between RRM2 and the cell cycle signaling pathway within LUAD. Targeting RRM2 inhibition effectively suppressed LUAD cell proliferation, migration, and invasion while promoting apoptosis. This intervention also modified the expression of several crucial proteins, including the downregulation of CDC25A, CDC25C, RAD1, Bcl-2, and PPM1D and the upregulation of TP53 and Bax (p < 0.05). Our findings highlight the potential utility of RRM2 expression as a biomarker for diagnosing and predicting prognosis in LUAD, shedding new light on the role of RRM2 in this malignancy.

Identifiants

pubmed: 38920074
pii: CGT-EPUB-141016
doi: 10.2174/0115665232286359240611051307
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Xiao-Jun Wang (XJ)

Department of Respiratory Medicine, Gansu Province People Hospital, Lanzhou, Gansu, PR China.

Yun-Xia Huo (YX)

Department of Neurological Surgery, The Second People Hospital of Lanzhou City, Lanzhou, Gansu, PR China.

Peng-Jun Yang (PJ)

Department of Internal Medicine, The Xigu Hospital of Lanzhou City, Lanzhou, Gansu, PR China.

Jing Gao (J)

Department of Respiratory Medicine, Gansu Province People Hospital, Lanzhou, Gansu, PR China.
Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Finland.

Wei-Dong Hu (WD)

Department of Respiratory Medicine, Gansu Province People Hospital, Lanzhou, Gansu, PR China.

Classifications MeSH