AMPK α1 Downregulates ROS Levels Through Regulating Trx Leading to Dysfunction of Apoptosis in Non-Small Cell Lung Cancer
Authors Gong D, Li Y, Wang Y, Chi B, Zhang J, Gu J, Yang J, Xu X, Hu S, Min L
Received 27 October 2019
Accepted for publication 17 May 2020
Published 23 June 2020 Volume 2020:13 Pages 5967—5977
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Takuya Aoki
Daohui Gong,1,* Ying Li,2,* Yuxiu Wang,1,* Beiyuan Chi,1 Jun Zhang,1 Jianjun Gu,1 JunJun Yang,1 Xingxiang Xu,1 Suwei Hu,3 Lingfeng Min1
1Department of Respiratory Medicine, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Department of Medical Oncology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Medical Genetic Center, Yangzhou Maternal and Child Health Care Service Centre, The Affiliated Hospital of Yangzhou University Medical College, Yangzhou, Jiangsu, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lingfeng Min
Department of Respiratory Medicine, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, People’s Republic of China
Medical Genetic Center, Yangzhou Maternal and Child Health Care Service Centre, The Affiliated Hospital of Yangzhou University Medical College, Yangzhou, Jiangsu 225002, People’s Republic of China
Purpose: AMP-activated protein kinase α 1 (AMPK α 1) associates closely with cancers. However, the relationship between AMPK α 1 and non-small cell lung cancer (NSCLC) is not fully understood. In this study, we aim to explore the role and mechanism of AMPK α 1 in NSCLC initiation and progression.
Materials and Methods: A total of 165 clinical NSCLC specimens were included in the formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays. The expression levels of AMPK α 1 and thioredoxin (Trx) in NSCLC cancer tissues and adjacent non-tumor lung tissues were measured through using immunohistochemistry. MTT assay was used to detect cell proliferation. Intracellular ROS levels were measured by using H2DCFDA reagent. Lentiviruses including LV-PRKAA1-RNAi, LV-PRKAA1 and a negative LV-control were used to infect A549 cells to modulate AMPK α 1 expression in vitro. Immunoblotting was used to determine the modulation relationship between AMPK α 1 and Trx. Log rank test and Kaplan–Meier survival analysis were performed to evaluate the significances of AMPK α 1 and Trx expression levels on NSCLC patients’ prognoses.
Results: AMPK α 1 was highly expressed in NSCLC cancer tissues and correlated with poor prognosis in patients with NSCLC. In A549 cells, overexpression of AMPK α 1 promoted proliferation, suppressed ROS levels and inhibited apoptosis. Moreover, inhibition of AMPK α 1 expression achieved the opposite effects. Trx was significantly overexpressed in NSCLC cancer tissues; furthermore, Trx expressed much more in cytoplasm when compared with cell nucleus. Trx expression levels were positively correlated with AMPK α 1 expression levels in NSCLC tissues. AMPK α 1 could regulate Trx in A549 cells. No significant correlations were observed between Trx expression variances and prognoses in NSCLC patients. Combination of AMPK α 1 and Trx had no advantage in predicting prognoses of NSCLC patients.
Conclusion: These results suggest that AMPK α 1 serves a carcinogenic role at least in part through the regulation of Trx expression, and thus represents a potential treatment target in patients with NSCLC.
Keywords: AMPK α 1, ROS, apoptosis, non-small cell lung cancer
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