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首页> 外文期刊>Cellular Signalling >piR-31470 epigenetically suppresses the expression of glutathione S-transferase pi 1 in prostate cancer via DNA methylation
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piR-31470 epigenetically suppresses the expression of glutathione S-transferase pi 1 in prostate cancer via DNA methylation

机译：PiR-31470简要抑制了通过DNA甲基化在前列腺癌中谷胱甘肽S-转移酶PI1的表达

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摘要

Inactivation of glutathione S-transferase pi 1 (GSTP1) via hypermethylation is an early and common event in prostate carcinogenesis. Functional inactivation of GSTP1 increases the susceptibility to oxidative stress and enhance progression risk of the prostatic carcinoma. In this study, we hypothesized that the Piwi-interacting RNA (piRNA) could be a sequence-recognition and guidance molecule for induction of promoter methylation of GSTP1 facilitating prostate carcinogenesis. We found that piR-31470 was highly expressed in prostate cancer cells, and piR-31470 could bind to piwi-like RNA-mediated gene silencing 4 (PIWIL4) to form the PIWIL4/piR-31470 complex. This complex could bind to the nascent RNA transcripts of GSTPI, and recruit DNA methyltransferase 1, DNA methyltransferase 3 alpha and methyl-CpG binding domain protein 2 to initiate and maintain the hypermethylation and inactivation of GSTP1. Our data demonstrated that the overexpression of piR-31470 inhibited the levels of GSTP1 and increased vulnerability to oxidative stress and DNA damage in human prostate epithelial RWPE1 cells. In conclusion, this study characterized the roles of the PIWIL4/piR-31470 complex in the regulation of the transcription of GSTP1 by methylating the CpG island of GSTP1. This discovery may provide a novel therapeutic strategy by targeting piRNAs for the epigenetic treatment of prostate cancer.
机译：通过高甲基化灭活谷胱甘肽S-转移酶PI1（GSTP1）是前列腺发生中的早期和常见事件。 GSTP1的功能失活增加对氧化应激的敏感性，增强前列腺癌的进展风险。在该研究中，我们假设PIWI相互作用的RNA（PiRNA）可以是用于诱导促进前列腺癌的GSTP1启动子甲基化的序列识别和引导分子。我们发现PiR-31470在前列腺癌细胞中高度表达，PiR-31470可以与piwi样RNA介导的基因沉默4（Piwil4）结合以形成Piwil4 / PiR-31470络合物。该复合物可以与GSTPI的新生RNA转录物结合，并募集DNA甲基转移酶1，DNA甲基转移酶3α和甲基-CPG结合结构域蛋白2以引发和维持GSTP1的高甲基化和灭活。我们的数据表明，PIR-31470的过表达抑制了GSTP1的水平和对人前列腺上皮RWPE1细胞的氧化应激和DNA损伤的脆弱性增加。总之，该研究表征了PIWIL4 / PIR-31470复合物在通过甲基化GSTP1的CPG岛调节GSTP1的转录中的作用。该发现可以通过针对前列腺癌的表观遗传治疗靶向PIRNA来提供新的治疗策略。

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