Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level.
Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level.
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核miR-122在转录后水平直接调节细胞存活oncomiR miR-21的生物发生
DOI：
10.1093/nar/gkx1254
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发表时间：
2018-02-28
影响因子：
14.9
通讯作者：
Zen K
中科院分区：
文献类型：
--
作者：
Wang D;Sun X;Wei Y;Liang H;Yuan M;Jin F;Chen X;Liu Y;Zhang CY;Li L;Zen K
摘要肝脏miR-122可作为促凋亡因子抑制肿瘤的发生。然而，其基本机制仍然不完全清楚。本研究首次证明miR-122通过在转录后水平直接沉默癌细胞存活的生物发生oncomiR miR-21而促进肝癌细胞凋亡。我们发现，miR-122在原代肝细胞核中强烈表达，但其核定位在转化细胞中显着减少，特别是在化疗耐药肿瘤细胞中。miR-122和miR-21在肝细胞癌组织/细胞中呈负相关，增加或降低miR-122的核水平分别降低或增加miR-21的表达。在机制上，核miR-122通过与pri-miR-21的基底区中的含19-nt UG的识别元件结合并阻止Drosha-DGCR 8微处理器将pri-miR-21转化为pre-miR-21来抑制miR-21成熟。此外，体外和体内研究均表明，核miR-122通过调节miR-21靶向的程序性细胞死亡4（PDCD 4）信号通路参与HCC细胞凋亡的调控。
Abstract Hepatic miR-122 can serve as a pro-apoptotic factor to suppress tumorigenesis. The underlying mechanism, however, remains incompletely understood. Here we present the first evidence that miR-122 promotes hepatocellular carcinoma cell apoptosis through directly silencing the biogenesis of cell survival oncomiR miR-21 at posttranscriptional level. We find that miR-122 is strongly expressed in primary liver cell nucleus but its nuclear localization is markedly decreased in transformed cells particularly in chemoresistant tumor cells. MiRNA profiling and RT-qPCR confirm an inverse correlation between miR-122 and miR-21 in hepatocellular carcinoma tissues/cells, and increasing or decreasing nuclear level of miR-122 respectively reduces or increases miR-21 expression. Mechanistically, nuclear miR-122 suppresses miR-21 maturation via binding to a 19-nt UG-containing recognition element in the basal region of pri-miR-21 and preventing the Drosha-DGCR8 microprocessor's conversion of pri-miR-21 into pre-miR-21. Furthermore, both in vitro and in vivo studies demonstrate that nuclear miR-122 participates in the regulation of HCC cell apoptosis through modulating the miR-21-targeted programmed cell death 4 (PDCD4) signal pathway.
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DOI：
10.1261/rna.042911.113
发表时间：
2014-04
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Diaz JP;Chirayil R;Chirayil S;Tom M;Head KJ;Luebke KJ
通讯作者：
Luebke KJ
影响因子：
4.5
作者：
Jeffries, Clark D.;Fried, Howard M.;Perkins, Diana O.
通讯作者：
Perkins, Diana O.
影响因子：
64.5
作者：
Han, Jinju;Lee, Yoontae;Kim, V. Narry
通讯作者：
Kim, V. Narry
影响因子：
64.8
作者：
Davis, Brandi N.;Hilyard, Aaron C.;Hata, Akiko
通讯作者：
Hata, Akiko
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM