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Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression.
Cancer Letters ( IF 9.7 ) Pub Date : 2020-08-28 , DOI: 10.1016/j.canlet.2020.08.036
Wen Peng 1 , Chuan Zhang 1 , Jianing Peng 2 , Yuanjian Huang 1 , Chaofan Peng 1 , Yuqian Tan 1 , Dongjian Ji 1 , Yue Zhang 1 , Dongsheng Zhang 1 , Junwei Tang 1 , Yifei Feng 1 , Yueming Sun 1
Affiliation  

The mitogen activated protein kinase (MAPK) pathway has been reported to be involved in many cancer developments. Normally, MAPK activity is self-limited between rapid phosphorylation and dephosphorylation. In abnormal conditions, however, this dynamic equilibrium is broken, trigging tumor-suppressing or -promoting roles. While dual-specificity MAPK phosphatases (MKP/DUSPs) are important for cascade control in MAPK pathway, their role in colorectal cancer (CRC) remains largely unknown. Here, we investigated lnc-FAM84B-4 and DUSP1 to systematically elucidate their underlying roles in MAPK singling pathway and functions in CRC. Upregulated lnc-FAM84B-4 was identified by re-mining CRC microarray. Functional assays were performed in vitro and in vivo. RNA-Seq, RNA pull-down, and RIP assays were used to investigate the mechanisms of Lnc-FAM84B-4 in regulating expression of DUSP1. The results indicated that Lnc-FAM84B-4 regulates MAPK pathway by restraining DUSP1 expression. Mechanistically, RNA pull-down followed by mass spectrum determined hnRNPK functions as a binding partner of lnc-FAM84B-4 in mediating DUSP1 expression. Our findings demonstrate the important role of lnc-FAM84B-4-hnRNPK-DUSP1 axis in CRC development, and suggest a therapeutic target for CRC treatment.



中文翻译:

Lnc-FAM84B-4通过与蛋白hnRNPK相互作用来抑制MAPK磷酸酶-DUSP1表达,从而成为致癌的lncRNA。

据报道,有丝分裂原活化的蛋白激酶(MAPK)通路参与了许多癌症的发展。通常,MAPK活性在快速磷酸化和去磷酸化之间是自我限制的。然而,在异常情况下,这种动态平衡被打破,触发了肿瘤抑制或促进作用。虽然双特异性MAPK磷酸酶(MKP / DUSPs)对于MAPK途径中的级联控制很重要,但它们在结直肠癌(CRC)中的作用仍然未知。在这里,我们研究了lnc-FAM84B-4和DUSP1,以系统地阐明它们在MAPK信号通路和CRC中的潜在作用。通过重新挖掘CRC微阵列鉴定出上调的lnc-FAM84B-4。功能测定在体外体内进行。RNA-Seq,RNA下拉和RIP分析用于研究Lnc-FAM84B-4调节DUSP1表达的机制。结果表明,Lnc-FAM84B-4通过抑制DUSP1表达来调节MAPK途径。从机理上讲,RNA下拉检测后由质谱确定,hnRNPK在介导DUSP1表达中作为lnc-FAM84B-4的结合伴侣起作用。我们的发现证明了lnc-FAM84B-4-hnRNPK-DUSP1轴在CRC发育中的重要作用,并提出了CRC治疗的治疗目标。

更新日期:2020-09-09
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