Opposing roles of C/EBPα and eEF1A1 in Sp1-regulated miR-122 transcription

作     者：Zeng, Chunxian Sang, Ye Wang, Feng-Yi Zhuang, Shi-Mei 

作者机构：Sun Yat Sen Univ MOE Key Lab Gene Funct & Regulat State Key Lab Biocontrol Sch Life SciInnovat Ctr Canc Med Guangzhou Peoples R China Sun Yat Sen Univ Key Lab Liver Dis Guangdong Prov Affiliated Hosp 3 Guangzhou Peoples R China 

出 版 物：《RNA BIOLOGY》 (核糖核酸生物学)

年 卷 期：2020年第17卷第2期

页      面：202-210页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：National Key R&D Program of China [2017YFA0504402] National Natural Science Foundation of China [91440205, 81201631, 81930076] Fundamental Research Funds for the Central Universities [171gjc32] Science and Information Technology of Guangzhou Natural Science Foundation of Guangdong Province [2018A0303130241] Science and Technology Project of Shenzhen [JCYJ20170307143928246] 

主　　题：Noncoding RNA miRNA miR-122 Sp1 C/EBP alpha eEF1A1 

摘      要：We previously showed that miR- 122 was frequently downregulated in hepatocellular carcinoma (HCC) and C/EBP alpha transactivated miR-122 expression. In this study, we found that Sp1 bound to the miR-122 promoter at two different sites. Interestingly, either inhibition or overexpression of Sp1 could decrease the miR-122 promoter activity and the cellular miR-122 level in hepatoma cells. Further investigations disclosed that Sp1 cooperated with C/EBP alpha to induce miR- 122 transcription by binding to the positive regulatory site D in the miR-122 promoter, whereas eEF1A1 interacted with Sp1 to bind to the negative regulatory site E and inhibit miR-122 transcription. Significantly, both Sp1 and eEF1A1 levels were enhanced, but C/EBP alpha and miR-122 expression were reduced in HCC tissues. Knockdown of eEF1A1 enhanced miR-122 level and inhibited cell growth, and these effects were abrogated when Sp1 was silenced. Consistently, the promoter activity enhanced by site E deletion was attenuated by silencing Sp1. Moreover, reduction of miR-122 resulted from Sp1 overexpression was rescued by coexpressing C/EBP alpha. These data suggest that C/EBP alpha and eEF1A1 may play opposing roles in Sp1-regulating miR-122 transcription, and the eEF1A1 upregulation accompanied by C/EBP alpha downregulation in HCC may switch the regulatory functions of Sp1 and led to reduced miR-122 transcription. These findings highlight the complex regulatory network of miR- 122 expression and its significance in hepatocarcinogenesis.