PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma

Background: The role of Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) in tumorigenesis and development has been extensively studied. As we previously demonstrated, PinX1 plays an important role in modulating epithelial-mesenchymal transition (EMT), stemness, cell prolifer...

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Main Authors: Mengxue Yang, Fang Chen, Chaosheng Yu, Zhimou Cai, Qingwen Zhong, Jialian Feng, Guanxue Li, Congxiang Shen, Zhong Wen
Format: Article
Language:English
Published: IMR Press 2023-08-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808170
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author Mengxue Yang
Fang Chen
Chaosheng Yu
Zhimou Cai
Qingwen Zhong
Jialian Feng
Guanxue Li
Congxiang Shen
Zhong Wen
author_facet Mengxue Yang
Fang Chen
Chaosheng Yu
Zhimou Cai
Qingwen Zhong
Jialian Feng
Guanxue Li
Congxiang Shen
Zhong Wen
author_sort Mengxue Yang
collection DOAJ
description Background: The role of Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) in tumorigenesis and development has been extensively studied. As we previously demonstrated, PinX1 plays an important role in modulating epithelial-mesenchymal transition (EMT), stemness, cell proliferation, and apoptosis in nasopharyngeal carcinoma (NPC). However, the relationship between PinX1, autophagy, and cell function in NPC remains unclear. This study aimed to investigate the mechanisms by which PinX1 regulates autophagy in NPC, and to explore its biological role and clinical significance in disease progression. Methods: The proliferative capacity of NPC cells was assessed by MTT and xenograft tumorigenicity assays. Autophagic flux was monitored using a tandem monomeric DAPI–FITC–LC3 reporter assay. The rates of apoptosis and the cell cycle in NPC cells were analyzed using flow cytometry. The activation of autophagy and the signaling status of the AKT/mTOR and NF-κB/p65 pathways were evaluated by Western blot analysis. Results: In addition to promoting autophagy and apoptosis, PinX1 overexpression suppressed proliferation, migration, invasion, and decelerated cell-cycle progression in NPC cells. These effects were reversed by inhibiting autophagy with 3-methyladenine. Mechanistic investigations clarified that PinX1 overexpression significantly reduced the expression of p-AKT, p-mTOR, p65, and p-p65. Chloroquine treatment in PinX1-overexpressing cells did not significantly alter p-AKT and p-mTOR levels, whereas 3-MA treatment in PinX1-overexpressing cells resulted in increased p65 and p-p65 expression, relative to untreated PinX1-overexpressing cells. Conclusions: It appears that PinX1 promotes autophagy by inhibiting the AKT/mTOR signaling pathway, which then inhibits NF-κB/p65 pathways, and consequently inhibiting cell proliferation and causing cell apoptosis in NPC cells.
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spelling doaj.art-64a3e6abb703471da9f7a403d9c2b3192023-09-04T09:13:42ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-08-0128817010.31083/j.fbl2808170S2768-6701(23)00830-4PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal CarcinomaMengxue Yang0Fang Chen1Chaosheng Yu2Zhimou Cai3Qingwen Zhong4Jialian Feng5Guanxue Li6Congxiang Shen7Zhong Wen8Department of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, Guangdong, ChinaBackground: The role of Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) in tumorigenesis and development has been extensively studied. As we previously demonstrated, PinX1 plays an important role in modulating epithelial-mesenchymal transition (EMT), stemness, cell proliferation, and apoptosis in nasopharyngeal carcinoma (NPC). However, the relationship between PinX1, autophagy, and cell function in NPC remains unclear. This study aimed to investigate the mechanisms by which PinX1 regulates autophagy in NPC, and to explore its biological role and clinical significance in disease progression. Methods: The proliferative capacity of NPC cells was assessed by MTT and xenograft tumorigenicity assays. Autophagic flux was monitored using a tandem monomeric DAPI–FITC–LC3 reporter assay. The rates of apoptosis and the cell cycle in NPC cells were analyzed using flow cytometry. The activation of autophagy and the signaling status of the AKT/mTOR and NF-κB/p65 pathways were evaluated by Western blot analysis. Results: In addition to promoting autophagy and apoptosis, PinX1 overexpression suppressed proliferation, migration, invasion, and decelerated cell-cycle progression in NPC cells. These effects were reversed by inhibiting autophagy with 3-methyladenine. Mechanistic investigations clarified that PinX1 overexpression significantly reduced the expression of p-AKT, p-mTOR, p65, and p-p65. Chloroquine treatment in PinX1-overexpressing cells did not significantly alter p-AKT and p-mTOR levels, whereas 3-MA treatment in PinX1-overexpressing cells resulted in increased p65 and p-p65 expression, relative to untreated PinX1-overexpressing cells. Conclusions: It appears that PinX1 promotes autophagy by inhibiting the AKT/mTOR signaling pathway, which then inhibits NF-κB/p65 pathways, and consequently inhibiting cell proliferation and causing cell apoptosis in NPC cells.https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808170nasopharyngeal carcinomaautophagic fluxmigrationakt/mtor pathway
spellingShingle Mengxue Yang
Fang Chen
Chaosheng Yu
Zhimou Cai
Qingwen Zhong
Jialian Feng
Guanxue Li
Congxiang Shen
Zhong Wen
PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma
Frontiers in Bioscience-Landmark
nasopharyngeal carcinoma
autophagic flux
migration
akt/mtor pathway
title PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma
title_full PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma
title_fullStr PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma
title_full_unstemmed PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma
title_short PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma
title_sort pinx1 promoted autophagy inhibits cell proliferation and induces cell apoptosis by inhibiting the nf κb p65 signaling pathway in nasopharyngeal carcinoma
topic nasopharyngeal carcinoma
autophagic flux
migration
akt/mtor pathway
url https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808170
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