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

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

  • EBioMedicine. 2020 Jan;51:102583. doi: 10.1016/j.ebiom.2019.11.044.
Yu Liu 1 Huan Li 2 Fan Liu 2 Li-Bin Gao 2 Rong Han 2 Chen Chen 2 Xue Ding 2 Shuang Li 2 Kun Lu 2 Ling Yang 2 Hui-Min Tian 2 Bin-Bin Chen 2 Xiao Li 2 Dong-Hui Xu 2 Xiao-Ling Deng 2 Song-Lin Shi 3
Affiliations

Affiliations

  • 1 Cancer Research Center, School of Medicine, Xiamen University, Room 303, No.4221-122, Xiang'annan Road, Xiang'an District, Xiamen 361102, PR China; School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, PR China.
  • 2 Cancer Research Center, School of Medicine, Xiamen University, Room 303, No.4221-122, Xiang'annan Road, Xiang'an District, Xiamen 361102, PR China.
  • 3 Cancer Research Center, School of Medicine, Xiamen University, Room 303, No.4221-122, Xiang'annan Road, Xiang'an District, Xiamen 361102, PR China. Electronic address: shisonglin@xmu.edu.cn.
Abstract

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.

Keywords

Breast cancer metastasis; Epithelial–mesenchymal transition; Heterogeneous nuclear ribonucleoprotein A2/B1; Profilin 2.

Figures
Products