MiR-122 directly inhibits human papillomavirus E6 gene and enhances interferon signaling through blocking suppressor of cytokine signaling 1 in SiHa cells.
MiR-122 directly inhibits human papillomavirus E6 gene and enhances interferon signaling through blocking suppressor of cytokine signaling 1 in SiHa cells.
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DOI：
10.1371/journal.pone.0108410
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
He J;Ji Y;Li A;Zhang Q;Song W;Li Y;Huang H;Qian J;Zhai A;Yu X;Zhao J;Shang Q;Wei L;Zhang F
人乳头瘤病毒（HPV）16感染被认为是导致宫颈癌的重要原因之一。病毒癌基因E6和E7的表达在癌症的发展中起重要作用。miR-122已被报道与肝炎病毒表现出很强的关系，并参与了几种肿瘤的发展，而miR-122对HPV感染和HPV病毒癌基因表达的影响仍有待研究。本研究利用RNAhybrid软件对miR-122与HPV 16 E6和E7 mRNA的潜在结合位点进行了鉴定。miR-122功能的过度和丧失表明miR-122可直接与HPV 16 E6 mRNA结合并显著抑制其在SiHa细胞中的表达，构建miR-122-E6-mu消除miR-122与E6的结合效应进一步证实了这一点。I型干扰素（IFN）及其经典效应分子的表达增加以及信号转导和转录激活因子（STAT 1）蛋白的磷酸化，提示miR-122可能增强了宫颈癌细胞中I型干扰素的表达，从而解释了HPV 16 E7和E6*I mRNA表达的显著降低。这可能是由于miR-122与细胞因子信号转导抑制因子1（SOCS 1）mRNA之间的结合，SOCS 1是干扰素信号转导途径的抑制因子。此外，经鉴定，miR-122在SOCS 1 mRNA中的结合位置为nt 359-nt 375。综上所述，本研究表明miR-122可以通过直接与E6 mRNA结合和促进SOCS 1依赖的IFN信号通路来有效抑制HPV 16。因此，miR-122可能作为抑制HPV感染的新的治疗选择。
Human Papillomavirus (HPV) 16 infection is considered as one of the significant causes of human cervical cancer. The expression of the viral oncogenes like E6 and E7 play an important role in the development of the cancer. MiR-122 has been reported to exhibit a strong relationship with hepatitis viruses and take part in several tumor development, while the effects of miR-122 on HPV infection and the HPV viral oncogenes expression still remain unexplored. In this study, using RNAhybrid software, the potential binding sites between miR-122 and HPV16 E6 and E7 mRNAs were identified. Over and loss of miR-122 function showed that miR-122 could directly bind with HPV16 E6 mRNA and significantly inhibit its expression in SiHa cells, which was further confirmed by constructing the miR-122-E6-mu to eliminate the miR-122 binding effects with E6. The increase of the expression of type I interferon (IFN) and its classical effective molecules and the phosphorylation of signal transducers and activators of transcription (STAT1) protein indicated that miR-122 might enhance type I interferon in cervical carcinoma cells, which explained the significant reduction of HPV16 E7 and E6*I mRNA expression. This might be due to the binding between miR-122 and suppressor of cytokine signaling 1 (SOCS1) mRNA, which is the suppressor of interferon signaling pathway. Moreover, it was identified that the miR-122 binding position was nt359-nt375 in SOCS1 mRNA. Taken together, this study indicated that HPV16 could be effectively inhibited by miR-122 through both direct binding with E6 mRNA and promoting SOCS1-dependent IFN signaling pathway. Thus, miR-122 may serve as a new therapeutic option for inhibiting HPV infection.
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影响因子：
3.3
作者：
Scaria V;Hariharan M;Maiti S;Pillai B;Brahmachari SK
通讯作者：
Brahmachari SK
影响因子：
3.7
作者：
Chiantore MV;Vannucchi S;Accardi R;Tommasino M;Percario ZA;Vaccari G;Affabris E;Fiorucci G;Romeo G
通讯作者：
Romeo G
影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
MiR-122 通过阻断细胞因子信号传导抑制因子 1 来调节 I 型干扰素表达
DOI：
10.1016/j.biocel.2013.01.008
发表时间：
2013-04-01
影响因子：
4
作者：
Li, Aimei;Song, Wuqi;Zhang, Fengmin
通讯作者：
Zhang, Fengmin
影响因子：
3.9
作者：
Haller, Otto;Staeheli, Peter;Kochs, Georg
通讯作者：
Kochs, Georg