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Sci Rep:miRNA-302s可能是人类睾丸生殖细胞瘤的致瘤基因

2019-07-11 AlexYang MedSci原创

在世界大部分范围内,睾丸生殖细胞瘤(TGCT)是年轻男性最常见的恶性肿瘤,但是其中的病因学仍旧未知。研究人员已经鉴定了多个TGCT易感位点,并且已经阐释了SPRY4可能是TGCT的一个致瘤基因。更多的是,其中的许多位点为基因组的非编码区域。miRNA在TGCT和正常睾丸中的差异表达之前已有报道。最近,有研究人员使用qPCR的方法来分析正常和恶性睾丸组织中,10个miRNA的表达情况,这10个miR

在世界大部分范围内,睾丸生殖细胞瘤(TGCT)是年轻男性最常见的恶性肿瘤,但是其中的病因学仍旧未知。

研究人员已经鉴定了多个TGCT易感位点,并且已经阐释了SPRY4可能是TGCT的一个致瘤基因。更多的是,其中的许多位点为基因组的非编码区域。miRNA在TGCT和正常睾丸中的差异表达之前已有报道。最近,有研究人员使用qPCR的方法来分析正常和恶性睾丸组织中,10个miRNA的表达情况,这10个miRNAs是研究人员通过测序的方法鉴定的在TGCT中上调最高的miRNA。研究发现,miR-302a-3p、miR-302b-3p和miR-302c-3p在铂化疗的TGCT细胞系NT2-D1和833?K中下调。通过使用miRNA抑制剂调节的瞬时转染,研究人员成功的抑制了miR-20家族3个成员的表达。对miRNA-302s的抑制导致了NT2-D1细胞中细胞增殖减少,但是在833K细胞中无上述情况。在2个细胞系中,miRNA-302s的抑制能够导致SPRY4表达的减少,而SPRY4能够调控MAPK/ERK和PI3K/Akt信号途径。miR-302b-3p和miR-302c-3p的抑制能够减少ERK1/2的磷酸化,而miR-302a-3p和miR-302b-3p的抑制能够导致细胞凋亡抑制因子和存活素表达的下调。

最后,研究人员指出,miRNA-302s能够通过诱导SPRY4的表达和激活MAPK/ERK途径作为TGCT的致瘤基因,并能增加生存素的表达来抑制细胞凋亡。

原始出处:

Mrinal K. Das, Herman S. F. Evensen, Kari Furu et al. miRNA-302s may act as oncogenes in human testicular germ cell tumours. Sci Rep. 24 Jun 2019

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    2019-11-18 smallant2002
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    2019-07-13 Homburg
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    2019-07-13 zhangph
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