MUC3A promotes non-small cell lung cancer progression via activating the NFκB pathway and attenuates radiosensitivity.
MUC3A promotes non-small cell lung cancer progression via activating the NFκB pathway and attenuates radiosensitivity.
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MUC3A 通过激活 NFκB 通路并减弱放射敏感性促进非小细胞肺癌进展
DOI：
10.7150/ijbs.59430
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发表时间：
2021
影响因子：
9.2
通讯作者：
Xie C
中科院分区：
文献类型：
--
作者：
Sun Y;Sun X;You C;Ma S;Luo Y;Peng S;Tang F;Tian X;Wang F;Huang Z;Yu H;Xiao Y;Wang X;Zhang J;Gong Y;Xie C
粘蛋白3A（MUC 3A）在非小细胞肺癌（NSCLC）中高表达，但其功能和对临床预后的影响尚不清楚。92例非小细胞肺癌组织芯片显示高水平的MUC 3A与预后差、晚期分期和低分化相关。MUC 3A基因敲低可显著抑制NSCLC细胞增殖，并通过下调细胞周期检查点诱导G1/S期积累。MUC 3A敲低也抑制体内肿瘤生长，并与辐射具有协同效应。MUC 3A敲低增加了NSCLC细胞中辐射诱导的DNA双链断裂和γ-H2 AX磷酸化。MUC 3A下调可抑制BRCA-1/RAD 51通路和P53、XCRR 6的核转位，提示MUC 3A促进DNA损伤修复，降低辐射敏感性。MUC 3A基因敲低也导致体内RELA和P53的核转位减少。免疫沉淀结果显示MUC 3A与RELA相互作用，通过促进RELA磷酸化和干扰RELA与IκB的结合，激活NFκB B通路。我们的研究表明，MUC 3A是一个潜在的致癌基因，并与不利的临床结果。MUC 3A水平高的NSCLC患者，应更频繁地随访，可能从放疗中获益较少。
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 in vivo 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 in vivo. 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.
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影响因子：
10.3
作者：
LECHEVALIER, T;ARRIAGADA, R;LAPLANCHE, A
通讯作者：
LAPLANCHE, A
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.
影响因子：
5.1
作者：
Lee, Jae-Chul;Tae, Hyun-Jin;Bae, Eun Joo
通讯作者：
Bae, Eun Joo
影响因子：
6.4
作者：
Barbano, Raffaela;Copetti, Massimiliano;Parrella, Paola
通讯作者：
Parrella, Paola
影响因子：
--
作者：
Li, Yanjing;Sui, Hong;Bai, Yuxian
通讯作者：
Bai, Yuxian