Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways

被引：40

作者：

Liu, Yu ^{[1
,2
]}

Li, Huan ^{[1
]}

Liu, Fan ^{[1
]}

Gao, Li-Bin ^{[1
]}

Han, Rong ^{[1
]}

Chen, Chen ^{[1
]}

Ding, Xue ^{[1
]}

Li, Shuang ^{[1
]}

Lu, Kun ^{[1
]}

Yang, Ling ^{[1
]}

Tian, Hui-Min ^{[1
]}

Chen, Bin-Bin ^{[1
]}

Li, Xiao ^{[1
]}

Xu, Dong-Hui ^{[1
]}

Deng, Xiao-Ling ^{[1
]}

Shi, Song-Lin ^{[1
]}

机构：

[1] Xiamen Univ, Canc Res Ctr, Sch Med, Room 303,4221-122 Xiangannan Rd, Xiamen 361102, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai 200240, Peoples R China

来源：

EBIOMEDICINE | 2020年 / 51卷

基金：

中国国家自然科学基金;

关键词：

Heterogeneous nuclear ribonucleoprotein A2/B1; Breast cancer metastasis; Epithelial-mesenchymal transition; Profilin; 2; EPITHELIAL-MESENCHYMAL TRANSITION; HNRNP; EXPRESSION; PROFILIN-2; MECHANISMS; PROTEINS; TARGETS; BINDING; TISSUE; ACTIN;

D O I：

10.1016/j.ebiom.2019.11.044

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear. Methods: The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models. Findings: In contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3'-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA. Interpretation: Our data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments. (C) 2019 The Authors. Published by Elsevier B.V.

引用

页数：14

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