MUC3A promotes non-small cell lung cancer progression via activating the NFκB pathway and attenuates radiosensitivity

Mucin 3A (MUC3A) is highly expressed in non-small cell lung cancer (NSCLC), but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 NSCLC samples indicated that high levels of MUC3A were associated with poor prognosis, advanced staging, and low differentia...

Full description

Saved in:
Bibliographic Details
Published in:International journal of biological sciences 2021-01, Vol.17 (10), p.2523-2536
Main Authors: Sun, Yingming, Sun, Xiaoge, You, Chengcheng, Ma, Shijing, Luo, Yuan, Peng, Shan, Tang, Fang, Tian, Xiaoli, Wang, Feng, Huang, Zhengrong, Yu, Hongnv, Xiao, Yu, Wang, Xiaoyong, Zhang, Junhong, Gong, Yan, Xie, Conghua
Format: Article
Language:English
Subjects:
Adenoviruses
Animals
Antibodies
Autophagy
Binding sites
Biomarkers
BRCA1 protein
Breast cancer
Carcinoma, Non-Small-Cell Lung - genetics
Cell cycle
Cell Cycle Checkpoints - genetics
Cell growth
Cell Line, Tumor
Cell proliferation
Cell Proliferation - genetics
Deoxyribonucleic acid
DNA
DNA Breaks, Double-Stranded - radiation effects
DNA damage
DNA microarrays
DNA repair
DNA Repair - genetics
DNA Repair - radiation effects
Female
Humans
I-kappa B Proteins - metabolism
Immunoprecipitation
Lung cancer
Lung Neoplasms - genetics
Male
Medical prognosis
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Mucin
Mucin-3 - genetics
NF-κB protein
Non-small cell lung carcinoma
Nuclear Proteins
Nuclei (cytology)
Phosphorylation
Proteins
Radiation
Radiation damage
Radiation effects
Radiation therapy
Radiation Tolerance - genetics
Radiosensitivity
Reagents
Research Paper
Signal Transduction - genetics
Signal Transduction - radiation effects
Small cell lung carcinoma
Synergistic effect
Transcription Factor RelA - metabolism
Translocation
Tumors
Xenograft Model Antitumor Assays
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mucin 3A (MUC3A) is highly expressed in non-small cell lung cancer (NSCLC), but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 NSCLC samples indicated that high levels of MUC3A were associated with poor prognosis, advanced staging, and low differentiation. MUC3A knockdown significantly suppressed NSCLC cell proliferation and induced G1/S accumulation via downregulating cell cycle checkpoints. MUC3A knockdown also inhibited tumor growth and had synergistic effects with radiation. MUC3A knockdown increased radiation-induced DNA double strain breaks and γ-H2AX phosphorylation in NSCLC cells. MUC3A downregulation inhibited the BRCA-1/RAD51 pathway and nucleus translocation of P53 and XCRR6, suggesting that MUC3A promoted DNA damage repair and attenuated radiation sensitivity. MUC3A knockdown also resulted in less nucleus translocation of RELA and P53 . Immunoprecipitation revealed that MUC3A interacted with RELA and activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. Our studies indicated that MUC3A was a potential oncogene and associated with unfavorable clinical outcomes. NSCLC patients with a high MUC3A level, who should be more frequent follow-up and might benefit less from radiotherapy.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.59430