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Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways.
EBioMedicine ( IF 9.7 ) Pub Date : 2020-01-02 , 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 2
EBioMedicine ( IF 9.7 ) Pub Date : 2020-01-02 , 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 2
Affiliation
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.
中文翻译：
通过维持多种基因和途径的平衡，异质核糖核蛋白A2 / B1是人类乳腺癌转移的负调节剂。
背景技术异质核核糖核蛋白（hnRNP）A2 / B1是一种重要的RNA结合蛋白，可影响许多基因的RNA加工，剪接，转运和稳定性。hnRNPA2 / B1在各种癌症类型的增殖和转移过程中表达，并促进此类过程。然而，hnRNPA2 / B1在乳腺癌中的确切作用和机制尚不清楚。方法使用组织芯片，小鼠模型和公开数据评估hnRNPA2 / B1与乳腺癌转移的关系。在细胞系和小鼠模型中研究了hnRNPA2 / B1在乳腺癌转移中的作用和机制。结果与其他癌症研究发现相反，hnRNPA2 / B1表达与乳腺癌转移呈负相关。hnRNPA2 / B1在体外和体内均抑制MDA-MB-231三阴性乳腺癌（TNBC）细胞转移。hnRNPA2 / B1敲除激活了ERK-MAPK / Twist和GR-beta / TCF4通路，但抑制了STAT3和WNT / TCF4信号通路。Profilin 2（PFN2）促进乳腺癌细胞迁移和侵袭，而hnRNPA2 / B1直接与PFN2 mRNA 3'-非翻译区中的UAGGG基因座结合，并降低PFN2 mRNA的稳定性。解释我们的数据支持hnRNPA2 / B1在乳腺癌患者的肿瘤转移风险和生存预测中的作用。hnRNPA2 / B1在转移中的抑制作用是下游多个基因和信号通路的平衡。hnRNPA2 / B1对PFN2的下调可能部分解释了hnRNPA2 / B1在乳腺癌转移中的抑制机制。因此，
更新日期：2020-01-04
中文翻译：
通过维持多种基因和途径的平衡，异质核糖核蛋白A2 / B1是人类乳腺癌转移的负调节剂。
背景技术异质核核糖核蛋白（hnRNP）A2 / B1是一种重要的RNA结合蛋白，可影响许多基因的RNA加工，剪接，转运和稳定性。hnRNPA2 / B1在各种癌症类型的增殖和转移过程中表达，并促进此类过程。然而，hnRNPA2 / B1在乳腺癌中的确切作用和机制尚不清楚。方法使用组织芯片，小鼠模型和公开数据评估hnRNPA2 / B1与乳腺癌转移的关系。在细胞系和小鼠模型中研究了hnRNPA2 / B1在乳腺癌转移中的作用和机制。结果与其他癌症研究发现相反，hnRNPA2 / B1表达与乳腺癌转移呈负相关。hnRNPA2 / B1在体外和体内均抑制MDA-MB-231三阴性乳腺癌（TNBC）细胞转移。hnRNPA2 / B1敲除激活了ERK-MAPK / Twist和GR-beta / TCF4通路，但抑制了STAT3和WNT / TCF4信号通路。Profilin 2（PFN2）促进乳腺癌细胞迁移和侵袭，而hnRNPA2 / B1直接与PFN2 mRNA 3'-非翻译区中的UAGGG基因座结合，并降低PFN2 mRNA的稳定性。解释我们的数据支持hnRNPA2 / B1在乳腺癌患者的肿瘤转移风险和生存预测中的作用。hnRNPA2 / B1在转移中的抑制作用是下游多个基因和信号通路的平衡。hnRNPA2 / B1对PFN2的下调可能部分解释了hnRNPA2 / B1在乳腺癌转移中的抑制机制。因此，
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