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Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma

BACKGROUND: Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is reco...

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Autores principales: Wu, Qian, Li, Rui, Wang, Qing-Xiang, Zhang, Meng-Yu, Liu, Ting-Ting, Qu, Yi-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171988/
https://www.ncbi.nlm.nih.gov/pubmed/35672776
http://dx.doi.org/10.1186/s12967-022-03457-w
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author Wu, Qian
Li, Rui
Wang, Qing-Xiang
Zhang, Meng-Yu
Liu, Ting-Ting
Qu, Yi-Qing
author_facet Wu, Qian
Li, Rui
Wang, Qing-Xiang
Zhang, Meng-Yu
Liu, Ting-Ting
Qu, Yi-Qing
author_sort Wu, Qian
collection PubMed
description BACKGROUND: Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD. METHODS: qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms. RESULTS: JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G(0)/G(1) phase and promoted apoptosis in LUAD cells. Mechanistically, silencing JAML repressed the process of epithelial-mesenchymal transition by inactivating the Wnt/β-catenin pathway in LUAD cells. Effects of JAML can be rescued by Wnt/β-catenin pathway activator in A549 cells. CONCLUSIONS: Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03457-w.
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spelling pubmed-91719882022-06-08 Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma Wu, Qian Li, Rui Wang, Qing-Xiang Zhang, Meng-Yu Liu, Ting-Ting Qu, Yi-Qing J Transl Med Research BACKGROUND: Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD. METHODS: qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms. RESULTS: JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G(0)/G(1) phase and promoted apoptosis in LUAD cells. Mechanistically, silencing JAML repressed the process of epithelial-mesenchymal transition by inactivating the Wnt/β-catenin pathway in LUAD cells. Effects of JAML can be rescued by Wnt/β-catenin pathway activator in A549 cells. CONCLUSIONS: Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03457-w. BioMed Central 2022-06-07 /pmc/articles/PMC9171988/ /pubmed/35672776 http://dx.doi.org/10.1186/s12967-022-03457-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wu, Qian
Li, Rui
Wang, Qing-Xiang
Zhang, Meng-Yu
Liu, Ting-Ting
Qu, Yi-Qing
Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma
title Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma
title_full Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma
title_fullStr Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma
title_full_unstemmed Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma
title_short Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma
title_sort junctional adhesion molecule-like protein promotes tumor progression via the wnt/β-catenin signaling pathway in lung adenocarcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171988/
https://www.ncbi.nlm.nih.gov/pubmed/35672776
http://dx.doi.org/10.1186/s12967-022-03457-w
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