Dysregulated NF-κB signal promotes the hub gene PCLAF expression to facilitate nasopharyngeal carcinoma proliferation and metastasis.


Journal

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295

Informations de publication

Date de publication:
May 2020
Historique:
received: 21 09 2019
revised: 22 12 2019
accepted: 30 12 2019
pubmed: 20 2 2020
medline: 22 12 2020
entrez: 20 2 2020
Statut: ppublish

Résumé

Nasopharyngeal carcinoma (NPC) is common in Southern China. The molecular mechanism underlying NPC genesis and progression has been comprehensively investigated, but the key gene (s) or pathway (s) pertaining to NPC are unidentified. We explored some key genes and pathways involved in NPC through using meta-analysis of deposited expression of microarray data of NPC. The expression of proliferating cell nuclear antigen clamp associated factor (PCLAF) was determined by real-time PCR and western blots. CCK-8 assay, colony formation assay, transwell migration assay, cell wound healing assay, cell cycle analysis and cell apoptosis were carried out to assess biological behaviors caused by downregulation and overexpression of PCLAF in vitro. CHIP was utilized to determine the direct upstream regulatory transcription factors of PCLAF. PCLAF was the key gene of NPC, which was significantly up-regulated in NPC cell line compared to the normal nasopharyngeal cell line. Additionally, in vitro assay has demonstrated the down-regulation and overexpression of PCLAF, resulted in significantly suppressed and enhanced NPC proliferation, metastasis and invasion respectively. Furthermore, the up-regulation of PCLAF in NPC is induced by direct binding of dysregulated NF-κB p50/RelB complex to the promoter of PCLAF. Our results offer a strategy for re-using the deposited data to find the key genes and pathways involved in pathogenesis of cancer. Our study has provided evidence of supporting the role of PCLAF in NPC genesis and progression.

Sections du résumé

BACKGROUND BACKGROUND
Nasopharyngeal carcinoma (NPC) is common in Southern China. The molecular mechanism underlying NPC genesis and progression has been comprehensively investigated, but the key gene (s) or pathway (s) pertaining to NPC are unidentified.
METHODS METHODS
We explored some key genes and pathways involved in NPC through using meta-analysis of deposited expression of microarray data of NPC. The expression of proliferating cell nuclear antigen clamp associated factor (PCLAF) was determined by real-time PCR and western blots. CCK-8 assay, colony formation assay, transwell migration assay, cell wound healing assay, cell cycle analysis and cell apoptosis were carried out to assess biological behaviors caused by downregulation and overexpression of PCLAF in vitro. CHIP was utilized to determine the direct upstream regulatory transcription factors of PCLAF.
RESULTS RESULTS
PCLAF was the key gene of NPC, which was significantly up-regulated in NPC cell line compared to the normal nasopharyngeal cell line. Additionally, in vitro assay has demonstrated the down-regulation and overexpression of PCLAF, resulted in significantly suppressed and enhanced NPC proliferation, metastasis and invasion respectively. Furthermore, the up-regulation of PCLAF in NPC is induced by direct binding of dysregulated NF-κB p50/RelB complex to the promoter of PCLAF.
CONCLUSION CONCLUSIONS
Our results offer a strategy for re-using the deposited data to find the key genes and pathways involved in pathogenesis of cancer. Our study has provided evidence of supporting the role of PCLAF in NPC genesis and progression.

Identifiants

pubmed: 32070873
pii: S0753-3322(20)30095-0
doi: 10.1016/j.biopha.2020.109905
pii:
doi:

Substances chimiques

DNA-Binding Proteins 0
NF-kappa B 0
PCLAF protein, human 0

Types de publication

Journal Article Meta-Analysis

Langues

eng

Sous-ensembles de citation

IM

Pagination

109905

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Auteurs

FeiFei Ma (F)

Department of Clinical Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Cheng Zhi (C)

Department of Clinical Pathology, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Minling Wang (M)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Tao Li (T)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, No. 1 Xincheng Road, Songshan Lake High-tech Industrial Development Zone, Dongguan, Guangdong 523808, China. Electronic address: taoliby@hotmail.com.

Shahzad Akbar Khan (SA)

Laboratory of Pathology, Department of Pathobiology, University of the Poonch, Rawalakot 12350, Pakistan.

Zhaoen Ma (Z)

Department of Clinical Earnosethroat, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Zhiliang Jing (Z)

Department of Clinical Pathology, The Affiliated Hospital of Guangdong Medical University, No. 57 Renmin Road, Zhanjiang, Guangdong 524001, China.

Chen Bo (C)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Qiang Zhou (Q)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Shaomei Xia (S)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Shiwen Huang (S)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Sicong Huang (S)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Zhiquan Zhang (Z)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Hongyun Jia (H)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China.

Xiaogang Cui (X)

Institutes of Biomedical Sciences, Shanxi University, No. 92 Wucheng Road, Taiyuan, Shanxi 030006, China.

Mingze Yao (M)

Institutes of Biomedical Sciences, Shanxi University, No. 92 Wucheng Road, Taiyuan, Shanxi 030006, China. Electronic address: Yaomz@sxu.edu.cn.

Tianxing Ji (T)

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China. Electronic address: jitianxing7021@163.com.

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Classifications MeSH