Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer
Authors Piao L, Li H, Feng Y, Li X, Cui Y, Xuan Y
Received 29 October 2019
Accepted for publication 2 February 2020
Published 6 March 2020 Volume 2020:12 Pages 1649—1660
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Sanjeev Srivastava
Lihua Piao,1 Haoyue Li,1,2 Ying Feng,1,2 Xiaogang Li,3 Yan Cui,4 Yanhua Xuan1,2
1Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, People’s Republic of China; 2Department of Pathology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, People’s Republic of China; 3Department of Urology, Yanbian University Affiliated Hospital, Yanji 133002, Jilin Province, People’s Republic of China; 4Department of Oncology, Yanbian University Affiliated Hospital, Yanji 133002, Jilin Province, People’s Republic of China
Correspondence: Yanhua Xuan
Department of Pathology, Yanbian University College of Medicine, No. 977, Gongyuan Road, Yanji City 133002, People’s Republic of China
Department of Oncology, Yanbian University Affiliated Hospital, No. 977, Gongyuan Road, Yanji City 133002, People’s Republic of China
Purpose: The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression.
Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffin-embedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting.
Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells.
Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.
Keywords: prostate cancer, leucine zipper-EF-hand containing transmembrane protein 1, epithelial-mesenchymal transition, prognosis
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]