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

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.