NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD

Zhuo, Ting; Wu, Zuotao; Chen, Sirong; Yang, Chuyi; Huang, Hongyu; Gan, Jinyan; Lyu, Jueqi; Xiao, Juan; Li, Zihao; Qin, Shouming; Wu, Yanbin

doi:10.7150/jca.91671

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Theranostics

Journal of Genomics

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J Cancer 2024; 15(9):2460-2474. doi:10.7150/jca.91671 This issue Cite

Research Paper

NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD

Ting Zhuo^1†, Zuotao Wu^2†, Sirong Chen^3†, Chuyi Yang¹, Hongyu Huang¹, Jinyan Gan¹, Jueqi Lyu¹, Juan Xiao⁴, Zihao Li^2✉, Shouming Qin^1✉, Yanbin Wu^1✉

1. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
2. Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
3. Department of Radiotherapy, Guangxi Medical University Cancer Hospital, No. 71 Hedi Rd, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
4. Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
† These authors contributed equally to this work.

✉ Corresponding authors: Yanbin Wu, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; Email address: yanbin_w2021com. Shouming Qin, Department of Pulmonary and More

Citation:

Zhuo T, Wu Z, Chen S, Yang C, Huang H, Gan J, Lyu J, Xiao J, Li Z, Qin S, Wu Y. NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD. J Cancer 2024; 15(9):2460-2474. doi:10.7150/jca.91671. https://www.jcancer.org/v15p2460.htm

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Abstract

Background: Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 1 (NEDD1) serves as a crucial factor in promoting cellular mitosis by directly facilitating wheel assembly and daughter centriole biogenesis at the lateral site of parent centrioles, ultimately driving centrosome replication. The amplification of centrosomes and the abnormal expression of centrosome-associated proteins contribute to the invasion and metastasis of non-small cell lung cancer cells. However, the specific mechanism by which NEDD1 contributes to the progression of lung adenocarcinoma (LUAD) remains unexplored. Therefore, the objective of this study is to uncover the role played by NEDD1 in LUAD.

Methods: To verify the expression of NEDD1 in pan-carcinoma. The feasibility of NEDD1 as a prognostic marker for LUAD in TCGA and GEO databases was verified. Subsequently, Cox proportional hazard regression analysis was used to screen the prognostic factors of LUAD, so as to analyze the correlation between prognostic factors and NEDD1 expression. For another, NEDD1-related genes were screened for pathway enrichment analysis to verify their possible functions. In addition, the expression of NEDD1 in LUAD was verified by qPCR and IHC, then siRNA was used to construct NEDD1-knocked lung cancer cells for subsequent cytobehavioral experiments. Finally, the distribution of NEDD1 in single-cell samples was revealed, and then the correlation between its overexpression and LUAD immune escape and drug resistance was analyzed.

Results: LUAD exhibits upregulation of NEDD1, which in turn promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, the overexpression of NEDD1 is closely associated with immune escape and drug resistance in LUAD.

Conclusion: NEDD1 serves as a reliable prognostic marker for LUAD, and its upregulation is associated with increased immune escape and drug resistance. Given these findings, NEDD1 holds potential as a novel therapeutic target for the treatment of LUAD.

Keywords: NEDD1, LUAD, cell proliferation, immune infiltration, drug resistance

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APA

Zhuo, T., Wu, Z., Chen, S., Yang, C., Huang, H., Gan, J., Lyu, J., Xiao, J., Li, Z., Qin, S., Wu, Y. (2024). NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD. Journal of Cancer, 15(9), 2460-2474. https://doi.org/10.7150/jca.91671.

ACS

Zhuo, T.; Wu, Z.; Chen, S.; Yang, C.; Huang, H.; Gan, J.; Lyu, J.; Xiao, J.; Li, Z.; Qin, S.; Wu, Y. NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD. J. Cancer 2024, 15 (9), 2460-2474. DOI: 10.7150/jca.91671.

NLM

CSE

Zhuo T, Wu Z, Chen S, Yang C, Huang H, Gan J, Lyu J, Xiao J, Li Z, Qin S, Wu Y. 2024. NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD. J Cancer. 15(9):2460-2474.

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