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内蒙古自治区呼和浩特市赛罕区大学西街235号 邮编: 010021
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.