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miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation

  • Authors:
    • Hua Fang
    • Weihua Wu
    • Zhijun Wu
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Fuxing Hospital, Capital Medical University, Beijing 100038, P.R. China, Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China, Department of Oncology, Ongniud Banner Hospital, Chifeng, Inner Mongolia Autonomous Region 024500, P.R. China
    Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 440
    |
    Published online on: May 11, 2022
       https://doi.org/10.3892/etm.2022.11367
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Abstract

Lung adenocarcinoma (LA), the primary histological type of non‑small cell lung cancer, is still incurable; its diagnosis and treatment remain a major clinical challenge. A previous study by our group examined the microRNA (miRNA/miR) expression profile in the extracellular vesicles from patients with LA and healthy controls and indicated that miR‑382‑3p levels were reduced in patients with LA. However, the precise roles of miR‑382‑3p in LA have so far remained elusive. In the present study, the miR‑382‑3p levels in tumor and adjacent non‑tumor control samples from 78 patients with LA were examined and it was identified that miR‑382‑3p expression was reduced in LA tumor samples compared with that in adjacent non‑tumor control tissues (P=0.022). Furthermore, miR‑382‑3p overexpression inhibited LA growth in a xenograft mouse model. Prediction results indicated that miR‑382‑3p may regulate protein ubiquitination and SUMOylation. Small ubiquitin‑like modifier (SUMO)1 activating enzyme subunit 1 (SAE1), one of the key components of the SUMO‑activating complex, was identified as a direct target of miR‑382‑3p via dual‑luciferase and immunoblotting assays. In patients with LA, miR‑382‑3p expression was negatively correlated with SAE1 protein levels (r=‑0.39, P<0.05) and higher SAE1 expression contributed to poor prognosis (P<0.01). Using immunoprecipitation, it was identified that miR‑382‑3p reduction‑induced SAE1 overexpression upregulated AKT SUMOylation, which further promoted AKT phosphorylation and activated the AKT signaling pathway. miR‑382‑3p inhibition promoted proliferation and inhibited apoptosis in LA cell lines, which was restored by SAE1 knockdown. In conclusion, the present study revealed that downregulation of miR‑382‑3p contributed to the carcinogenesis of LA via upregulation of SAE1 and promotion of AKT SUMOylation, providing a candidate target for LA treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Fang H, Wu W and Wu Z: miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation. Exp Ther Med 24: 440, 2022.
APA
Fang, H., Wu, W., & Wu, Z. (2022). miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation. Experimental and Therapeutic Medicine, 24, 440. https://doi.org/10.3892/etm.2022.11367
MLA
Fang, H., Wu, W., Wu, Z."miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation". Experimental and Therapeutic Medicine 24.1 (2022): 440.
Chicago
Fang, H., Wu, W., Wu, Z."miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation". Experimental and Therapeutic Medicine 24, no. 1 (2022): 440. https://doi.org/10.3892/etm.2022.11367
Copy and paste a formatted citation
x
Spandidos Publications style
Fang H, Wu W and Wu Z: miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation. Exp Ther Med 24: 440, 2022.
APA
Fang, H., Wu, W., & Wu, Z. (2022). miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation. Experimental and Therapeutic Medicine, 24, 440. https://doi.org/10.3892/etm.2022.11367
MLA
Fang, H., Wu, W., Wu, Z."miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation". Experimental and Therapeutic Medicine 24.1 (2022): 440.
Chicago
Fang, H., Wu, W., Wu, Z."miR‑382‑3p downregulation contributes to the carcinogenesis of lung adenocarcinoma by promoting AKT SUMOylation and phosphorylation". Experimental and Therapeutic Medicine 24, no. 1 (2022): 440. https://doi.org/10.3892/etm.2022.11367
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