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Journal Article Ppublish 5 citations

PubMed: 38920074 DOI: 10.2174/0115665232286359240611051307

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

Curr Gene Ther 25(2):136-156

Authors: Xiao-Jun Wang, Yun-Xia Huo, Peng-Jun Yang, Jing Gao, Wei-Dong Hu

Affiliations

  • Department of Respiratory Medicine, Gansu Province People Hospital, Lanzhou, Gansu, PR China.
  • Department of Neurological Surgery, The Second People Hospital of Lanzhou City, Lanzhou, Gansu, PR China.
  • Department of Internal Medicine, The Xigu Hospital of Lanzhou City, Lanzhou, Gansu, PR China.
  • Department of Respiratory Medicine, Gansu Province People Hospital, Lanzhou, Gansu, PR China. Department of Medicine, Respiratory Medicine Unit , Karolinska Institute, Stockholm, Sweden. Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

MeSH

Cells, Lung, Oxidoreductases, Ribonucleoside Diphosphate Reductase, Neoplasms, Adenocarcinoma, Adenocarcinoma Of Lung, Tissues, Genetic Therapy, Prognosis