FNDC5 and AKR1B10 inhibit the proliferation and metastasis of adrenocortical carcinoma cells by regulating AMPK/mTOR pathway

Chen,Danyan; Huang,Rongxi; Ren,Fang; Wang,Hongman; Wang,Chengjian; Zhang,Yu

doi:10.3892/etm.2023.11835

FNDC5 and AKR1B10 inhibit the proliferation and metastasis of adrenocortical carcinoma cells by regulating AMPK/mTOR pathway

Authors:
- Danyan Chen
- Rongxi Huang
- Fang Ren
- Hongman Wang
- Chengjian Wang
- Yu Zhang
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Affiliations: Department of Endocrinology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 401147, P.R. China, Department of Emergency, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 401147, P.R. China
Published online on: February 13, 2023 https://doi.org/10.3892/etm.2023.11835
Article Number: 136
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Being a rare malignancy, adrenocortical carcinoma (ACC) exhibits aggressiveness and poor prognosis. Fibronectin type III domain‑containing protein 5 (FNDC5) is a transmembrane protein involved in multiple types of cancer. Aldo‑keto reductase family 1 member B10 (AKR1B10) has a suppressive role in ACC. The present study aimed to investigate the role of FNDC5 in ACC cells as well as its mechanisms related to AKR1B10. The Gene Expression Profiling Interactive Analysis database predicted FNDC5 expression in tumour tissue of patients suffering from ACC and the overall survival rate. Western blotting as well as reverse transcription‑quantitative PCR were used for the examination of the transfection efficiency of FNDC5‑overexpression vector (Oe‑FNDC5) and small interfering (si)RNA against AKR1B10. Cell Counting Kit‑8 was employed for the assessment of cell viability. The proliferation, migration and invasion of the transfected cells were assessed by 5‑ethynyl‑2'‑deoxyuridine staining, wound healing and Transwell assays. Additionally, cell apoptosis was evaluated by flow cytometry and caspase‑3 activity was determined by ELISA. The levels of epithelial‑mesenchymal transition‑ and 5'‑AMP‑activated protein kinase (AMPK)/mTOR signalling pathway‑associated proteins were assessed by western blotting. The interaction between FNDC5 and AKR1B10 was confirmed by co‑immunoprecipitation. FNDC5 levels in ACC tissue were reduced compared with normal tissue. After overexpressing FNDC5, proliferation, migration and invasion of NCI‑H295R cells were suppressed, while cell apoptosis was promoted. FNDC5 interacted with AKR1B10 and AKR1B10 knockdown promoted proliferation, migration and invasion while inhibiting the apoptosis of NCI‑H295R cells transfected with si‑AKR1B10. The AMPK/mTOR signalling pathway was activated by FNDC5 overexpression, which was subsequently suppressed by AKR1B10 knockdown. Collectively, FNDC5 overexpression inhibited proliferation, migration and invasion while promoting apoptosis of NCI‑H295R cells via triggering the AMPK/mTOR signalling pathway. These effects were counteracted by AKR1B10 knockdown.

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